Is BID p.Arg125Lys (c.374G>A) pathogenic?

BID p.Arg125Lys (c.374G>A) is classified Uncertain significance in BID (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-20). AlphaMissense: likely benign (0.0871); Ultra-rare (popmax 0.0211%, mid).

How common is BID p.Arg125Lys (c.374G>A) in the general population?

BID p.Arg125Lys (c.374G>A) is ultra-rare (popmax 0.0211%, mid) (gnomAD).

What do computational predictors say about BID p.Arg125Lys (c.374G>A)?

AlphaMissense predicts likely benign (score 0.0871) — an in-silico prediction, not a clinical call.

BID p.Arg125Lys

c.374G>A · VCV3260928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0871 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0211%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0871	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -5.64	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 -3.6	GERP -2.2
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 0.061 · regional, not allelic
Overall
CADD	1.437	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 0.0211% Middle Eastern · 1/4,742 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00292% 47/1,610,452 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0211%	4,742
European (non-Finnish)	0.00373%	26,817
Remaining individualsnot grpmax-eligible	0.0016%	62,308
African / African-American	0.00134%	74,884

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: BID
Protein: p.Arg125Lys
Coding: c.374G>A
MANE Select: NM_001196
Type: single nucleotide variant
Location: chr22:17738219 (GRCh38)
Gene constraint: LOEUF 1.553 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.12 · 17 PDB
Residue 125: an α-helix

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

Similar variants

BID c.-14G>A Uncertain significance ★ same type
BID c.-15C>T Uncertain significance ★ same type
BID c.-23G>A Uncertain significance ★ same type
BID c.-24C>G Uncertain significance ★ same type
BID c.-33G>A Uncertain significance ★ same type
BID c.-39G>A Uncertain significance ★ same type
BID c.-59+698A>G Uncertain significance ★ same type
BID c.-59+722C>T 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/bid-p-arg125lys (accessed [today's date]).

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