Is IMPG2 p.Ala978Val (c.2933C>T) pathogenic?

IMPG2 p.Ala978Val (c.2933C>T) is classified Uncertain significance in IMPG2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-08-26). AlphaMissense: likely benign (0.2063); Rare (popmax 0.112%, amr); Associated with retinitis pigmentosa.

What condition is associated with IMPG2 p.Ala978Val (c.2933C>T)?

IMPG2 p.Ala978Val (c.2933C>T) is associated with retinitis pigmentosa (ClinVar).

How common is IMPG2 p.Ala978Val (c.2933C>T) in the general population?

IMPG2 p.Ala978Val (c.2933C>T) is rare (popmax 0.112%, amr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about IMPG2 p.Ala978Val (c.2933C>T)?

AlphaMissense predicts likely benign (score 0.2063) — an in-silico prediction, not a clinical call.

IMPG2 p.Ala978Val

c.2933C>T · rs371611480 · VCV901921

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2063 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.112%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.2063	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -6.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.112% Admixed American · 67/59,996 alleles

Filtering AF 0.0902% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0824%

Overall 0.019% 307/1,613,806 alleles · rare exomes 270/1,461,582 · genomes 37/152,224 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.112%	895
European (non-Finnish)	0.018%	5,565
Remaining individualsnot grpmax-eligible	0.016%	6,250
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,866
East Asian	0.00892%	11,216
South Asian	0.00769%	13,010
African / African-American	0.004%	25,000
Finnishnot grpmax-eligible	0.00156%	64,032

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: IMPG2
Protein: p.Ala978Val
Coding: c.2933C>T
MANE Select: NM_016247
dbSNP: rs371611480
Type: single nucleotide variant
Location: chr3:101242777 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 978: a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5); the sea 2 domain

Full IMPG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

IMPG2 p.Ala978Thr Uncertain significance ★★ ⚠ same residue
IMPG2 p.Ala978= Likely benign ★ same residue
IMPG2 p.Arg1088Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Trp758Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 c.*2658G>T Uncertain significance ★★ same condition
IMPG2 c.*426G>A Uncertain significance ★★ same condition
IMPG2 p.Ala1129Gly Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala698Val Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/impg2-p-ala978val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown