Is DEFB125 p.Ile3Val (c.7A>G) pathogenic?

DEFB125 p.Ile3Val (c.7A>G) is classified Uncertain significance in DEFB125 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-10). AlphaMissense: likely benign (0.1418); Very rare (popmax 0.00161%, nfe).

How common is DEFB125 p.Ile3Val (c.7A>G) in the general population?

DEFB125 p.Ile3Val (c.7A>G) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about DEFB125 p.Ile3Val (c.7A>G)?

AlphaMissense predicts likely benign (score 0.1418) — an in-silico prediction, not a clinical call.

DEFB125 p.Ile3Val

c.7A>G · VCV3271462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1418 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1418	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -6.55	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 0.23
Regional constraint	o/e 1.04	unconstrained · MANE · 8,704 bp · p 0.62 · regional, not allelic
Overall
CADD	3.319	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 0.00161% European (non-Finnish) · 19/1,179,228 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00118% 19/1,613,074 alleles · very rare

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: DEFB125
Protein: p.Ile3Val
Coding: c.7A>G
MANE Select: NM_153325
Type: single nucleotide variant
Location: chr20:87716 (GRCh38)
Gene constraint: LOEUF 1.526 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 63.59

Full DEFB125 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEFB125 p.Arg44Lys Uncertain significance ★ ⚠ same type
DEFB125 p.Arg50Gly Uncertain significance ★ ⚠ same type
DEFB125 p.Arg66Gln Uncertain significance ★ ⚠ same type
DEFB125 p.Cys39Tyr Uncertain significance ★ ⚠ same type
DEFB125 p.Glu143Gly Uncertain significance ★ ⚠ same type
DEFB125 p.Ile46Val Uncertain significance ★ ⚠ same type
DEFB125 p.Ile78Val Uncertain significance ★ ⚠ same type
DEFB125 p.Leu153Pro Uncertain significance ★ ⚠ 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/defb125-p-ile3val (accessed [today's date]).

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