Is INF2 p.Pro425Leu (c.1274C>T) pathogenic?

INF2 p.Pro425Leu (c.1274C>T) is classified Benign in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-12). AlphaMissense: likely benign (0.0795); Very rare (popmax 0.000246%, nfe).

How common is INF2 p.Pro425Leu (c.1274C>T) in the general population?

INF2 p.Pro425Leu (c.1274C>T) is very rare (popmax 0.000246%, nfe) (gnomAD).

What do computational predictors say about INF2 p.Pro425Leu (c.1274C>T)?

AlphaMissense predicts likely benign (score 0.0795) — an in-silico prediction, not a clinical call.

INF2 p.Pro425Leu

c.1274C>T · rs1555374270 · VCV439829

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0795 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000246%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0795	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -9.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.8	GERP 1.3, phastCons 0.001
Regional constraint	o/e 1.23	unconstrained · MANE · 929 bp · p 5.5e-05 · regional, not allelic
Overall
CADD	10.04	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 0.000246% European (non-Finnish) · 2/813,640 alleles

Filtering AF 4.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.5e-05%

Overall 0.000182% 2/1,096,494 alleles · very rare exomes 2/971,770 · genomes 0/124,724 · 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.Pro425Leu
Coding: c.1274C>T
MANE Select: NM_022489
dbSNP: rs1555374270
Type: single nucleotide variant
Location: chr14:104707541 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 425: the 'disordered' region

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

Similar variants

INF2 p.Pro425= Benign ★★ same residue
INF2 p.Pro425_Pro428del Benign/Likely benign ★★ same residue
INF2 p.Arg177Cys Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg214Cys Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg214His Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg218Gln Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg218Trp Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg91Gly Pathogenic/Likely pathogenic ★★ same type

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-pro425leu (accessed [today's date]).

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