Is INF2 p.Ala149Ser (c.445G>T) pathogenic?

INF2 p.Ala149Ser (c.445G>T) is classified Uncertain significance in INF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-02). AlphaMissense: likely benign (0.2826); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with INF2 p.Ala149Ser (c.445G>T)?

INF2 p.Ala149Ser (c.445G>T) is associated with Inborn genetic diseases (ClinVar).

How common is INF2 p.Ala149Ser (c.445G>T) in the general population?

INF2 p.Ala149Ser (c.445G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INF2 p.Ala149Ser (c.445G>T)?

AlphaMissense predicts likely benign (score 0.2826) — an in-silico prediction, not a clinical call.

INF2 p.Ala149Ser

c.445G>T · rs2504241604 · VCV1740772

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2826 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2826	likely benign
REVEL	0.7	pathogenic-leaning
SaProt	LLR -10.23	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 7.1, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 5,444 bp · p 1.4e-07 · regional, not allelic
Overall
CADD	25.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: INF2
Protein: p.Ala149Ser
Coding: c.445G>T
MANE Select: NM_022489
dbSNP: rs2504241604
Type: single nucleotide variant
Location: chr14:104703158 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 149: the gbd/fh3 domain

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.Ala149Val Uncertain significance ★★ ⚠ same residue
INF2 c.2418+3G>A Uncertain significance ★★ same condition
INF2 p.Ala1003Thr 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
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-ala149ser (accessed [today's date]).

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