Is INF2 p.Glu331Val (c.992A>T) pathogenic?

INF2 p.Glu331Val (c.992A>T) is classified Uncertain significance in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-06). AlphaMissense: likely benign (0.1351); Very rare (popmax 0.00224%, eas); Associated with Inborn genetic diseases.

What condition is associated with INF2 p.Glu331Val (c.992A>T)?

INF2 p.Glu331Val (c.992A>T) is associated with Inborn genetic diseases (ClinVar).

How common is INF2 p.Glu331Val (c.992A>T) in the general population?

INF2 p.Glu331Val (c.992A>T) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about INF2 p.Glu331Val (c.992A>T)?

AlphaMissense predicts likely benign (score 0.1351) — an in-silico prediction, not a clinical call.

INF2 p.Glu331Val

c.992A>T · rs773020110 · VCV3109644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1351 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1351	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.8	GERP 5.5, phastCons 0.96
Regional constraint	o/e 1.23	unconstrained · MANE · 929 bp · p 5.5e-05 · regional, not allelic
Overall
CADD	20.3	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 0.00224% East Asian · 1/44,740 alleles

Overall 6.21e-05% 1/1,609,056 alleles · very rare exomes 1/1,457,038 · genomes 0/152,018 · 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: INF2
Protein: p.Glu331Val
Coding: c.992A>T
MANE Select: NM_022489
dbSNP: rs773020110
Type: single nucleotide variant
Location: chr14:104707259 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB

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

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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
INF2 p.Arg852Trp 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-glu331val (accessed [today's date]).

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