Is INF2 p.Ala696Val (c.2087C>T) pathogenic?

INF2 p.Ala696Val (c.2087C>T) is classified Conflicting classifications of pathogenicity in INF2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-02-16). AlphaMissense: likely benign (0.1167); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with INF2 p.Ala696Val (c.2087C>T)?

INF2 p.Ala696Val (c.2087C>T) is associated with Inborn genetic diseases, focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Ala696Val (c.2087C>T) in the general population?

INF2 p.Ala696Val (c.2087C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about INF2 p.Ala696Val (c.2087C>T)?

AlphaMissense predicts likely benign (score 0.1167) — an in-silico prediction, not a clinical call.

INF2 p.Ala696Val

c.2087C>T · rs769120676 · VCV2467145

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1167 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1167	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -8.21	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 1.6	GERP 4.4, phastCons 0.89
Regional constraint	o/e 0.70	unconstrained · MANE · 3,038 bp · p 6.5e-07 · regional, not allelic
Overall
CADD	15.44	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 0.00167% Admixed American · 1/60,026 alleles

Overall 6.2e-05% 1/1,612,688 alleles · very rare exomes 1/1,460,404 · genomes 0/152,284 · 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.Ala696Val
Coding: c.2087C>T
MANE Select: NM_022489
dbSNP: rs769120676
Type: single nucleotide variant
Location: chr14:104709654 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 696: the fh2 domain; an α-helix

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

Also linked: focal segmental glomerulosclerosis 5 Charcot-Marie-Tooth disease dominant intermediate E

Similar variants

INF2 p.Ala696Gly Uncertain significance ★ ⚠ same residue
INF2 p.Arg177Cys Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg214Cys Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg214His Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg218Gln Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg218Trp Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg91Gly Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Asn202Asp Likely pathogenic ★★ 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-ala696val (accessed [today's date]).

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