Is IMPG1 p.Pro278Ser (c.832C>T) pathogenic?

IMPG1 p.Pro278Ser (c.832C>T) is classified Uncertain significance in IMPG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely benign (0.235); Very rare (popmax 8.87e-05%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with IMPG1 p.Pro278Ser (c.832C>T)?

IMPG1 p.Pro278Ser (c.832C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is IMPG1 p.Pro278Ser (c.832C>T) in the general population?

IMPG1 p.Pro278Ser (c.832C>T) is very rare (popmax 8.87e-05%, nfe) (gnomAD).

What do computational predictors say about IMPG1 p.Pro278Ser (c.832C>T)?

AlphaMissense predicts likely benign (score 0.235) — an in-silico prediction, not a clinical call.

IMPG1 p.Pro278Ser

c.832C>T · rs2481484529 · VCV3027860

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.235 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.87e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.235	likely benign
REVEL	0.567	indeterminate
SaProt	LLR -10.18	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 122 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.87e-05% European (non-Finnish) · 1/1,127,552 alleles

Overall 6.43e-05% 1/1,554,762 alleles · very rare exomes 1/1,402,536 · genomes 0/152,226 · joint denominator

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: IMPG1
Protein: p.Pro278Ser
Coding: c.832C>T
MANE Select: NM_001563
dbSNP: rs2481484529
Type: single nucleotide variant
Location: chr6:76011200 (GRCh38)
Gene constraint: LOEUF 1.217 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.26
Residue 278: the sea 1 domain

Full IMPG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IMPG1 c.498-1G>C Likely pathogenic ★★ same condition
IMPG1 p.Trp126Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG1 p.Arg580Cys Uncertain significance ★★ same condition
IMPG1 p.Glu695Lys Uncertain significance ★★ ⚠ same condition
IMPG1 p.His337Arg Uncertain significance ★★ ⚠ same condition
IMPG1 p.Leu268Ile Uncertain significance ★★ ⚠ same condition
IMPG1 p.Lys282Asn Uncertain significance ★★ ⚠ same condition
IMPG1 p.Met57Val 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/impg1-p-pro278ser (accessed [today's date]).

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