Is INF2 p.Asp997= (c.2991C>T) pathogenic?

INF2 p.Asp997= (c.2991C>T) is classified Likely benign in INF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-07-11). Very rare (popmax 0.00271%, nfe); Associated with Inborn genetic diseases.

What condition is associated with INF2 p.Asp997= (c.2991C>T)?

INF2 p.Asp997= (c.2991C>T) is associated with Inborn genetic diseases (ClinVar).

How common is INF2 p.Asp997= (c.2991C>T) in the general population?

INF2 p.Asp997= (c.2991C>T) is very rare (popmax 0.00271%, nfe) (gnomAD).

INF2 p.Asp997=

c.2991C>T · rs1057523828 · VCV390593

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7	GERP -6.2
Overall
CADD	0.476	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% European (non-Finnish) · 32/1,179,690 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00211% 34/1,612,120 alleles · very rare exomes 33/1,459,976 · genomes 1/152,144 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,865
East Asian	0.00223%	44,876
Remaining individualsnot grpmax-eligible	0.0016%	62,418

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: INF2
Protein: p.Asp997=
Coding: c.2991C>T
MANE Select: NM_022489
dbSNP: rs1057523828
Type: single nucleotide variant
Location: chr14:104713557 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 997: the 'disordered' region

Full INF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

INF2 p.Asp997Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
INF2 c.2418+3G>A Uncertain significance ★★ same condition
INF2 p.Ala1003Thr Uncertain significance ★★ ⚠ same condition
INF2 p.Ala149Ser Uncertain significance ★★ ⚠ same condition
INF2 p.Ala7Val Uncertain significance ★★ ⚠ same condition
INF2 p.Ala95Thr Uncertain significance ★★ same condition
INF2 p.Arg1075Cys Uncertain significance ★★ ⚠ same condition
INF2 p.Arg347Gln 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/inf2-p-asp997 (accessed [today's date]).

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