Is BLID p.Arg44His (c.131G>A) pathogenic?

BLID p.Arg44His (c.131G>A) is classified Uncertain significance in BLID (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely benign (0.0741); Ultra-rare (popmax 0.0293%, afr).

How common is BLID p.Arg44His (c.131G>A) in the general population?

BLID p.Arg44His (c.131G>A) is ultra-rare (popmax 0.0293%, afr) (gnomAD).

What do computational predictors say about BLID p.Arg44His (c.131G>A)?

AlphaMissense predicts likely benign (score 0.0741) — an in-silico prediction, not a clinical call.

BLID p.Arg44His

c.131G>A · rs769962172 · VCV2371435

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0741 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0293%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0741	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -6.96	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 0.068	GERP -2.5
Regional constraint	o/e 1.06	unconstrained · MANE · 323 bp · p 0.47 · regional, not allelic
Overall
CADD	6.226	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 0.0293% African / African-American · 22/75,026 alleles

Filtering AF 0.0198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00248% 40/1,613,820 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0293%	3,410
Middle Eastern	0.0165%	6,050
Admixed American	0.00666%	15,007
Finnishnot grpmax-eligible	0.00626%	15,967
South Asian	0.0011%	91,068
European (non-Finnish)	0.000678%	147,489

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: BLID
Protein: p.Arg44His
Coding: c.131G>A
MANE Select: NM_001001786
dbSNP: rs769962172
Type: single nucleotide variant
Location: chr11:122115792 (GRCh38)
Gene constraint: LOEUF 1.885 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 50.81

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

Similar variants

BLID p.Ala41Ser Uncertain significance ★ ⚠ same type
BLID p.Ala49Val Uncertain significance ★ ⚠ same type
BLID p.Arg31Gln Uncertain significance ★ ⚠ same type
BLID p.Asn54Lys Uncertain significance ★ ⚠ same type
BLID p.Asn54Ser Uncertain significance ★ ⚠ same type
BLID p.Cys101Arg Uncertain significance ★ ⚠ same type
BLID p.His13Tyr Uncertain significance ★ ⚠ same type
BLID p.His84Arg 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/blid-p-arg44his (accessed [today's date]).

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