Is BLMH p.Val211Ile (c.631G>A) pathogenic?

BLMH p.Val211Ile (c.631G>A) is classified Uncertain significance in BLMH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.0687); Very rare (popmax 0.00221%, sas).

How common is BLMH p.Val211Ile (c.631G>A) in the general population?

BLMH p.Val211Ile (c.631G>A) is very rare (popmax 0.00221%, sas) (gnomAD).

What do computational predictors say about BLMH p.Val211Ile (c.631G>A)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

BLMH p.Val211Ile

c.631G>A · VCV4212359

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.79	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 -2.2	GERP -5.4
Regional constraint	o/e 0.84	unconstrained · MANE · 39 kb · p 0.0015 · regional, not allelic
Overall
CADD	1.318	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 0.00221% South Asian · 2/90,324 alleles

Filtering AF 0.000368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000138%

Overall 0.000497% 8/1,610,698 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00221%	45,162
Remaining individualsnot grpmax-eligible	0.0016%	62,360
African / African-American	0.00134%	74,788
European (non-Finnish)	0.000339%	294,612

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: BLMH
Protein: p.Val211Ile
Coding: c.631G>A
MANE Select: NM_000386
Type: single nucleotide variant
Location: chr17:30285402 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 98.10 · 6 PDB
Residue 211: an α-helix

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

Similar variants

BLMH p.Ala117Gly Uncertain significance ★ ⚠ same type
BLMH p.Ala13Val Uncertain significance ★ ⚠ same type
BLMH p.Ala313Val Uncertain significance ★ ⚠ same type
BLMH p.Ala314Ser Uncertain significance ★ ⚠ same type
BLMH p.Ala314Val Uncertain significance ★ ⚠ same type
BLMH p.Arg191Leu Uncertain significance ★ ⚠ same type
BLMH p.Arg43Trp Uncertain significance ★ same type
BLMH p.Arg72Gln 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/blmh-p-val211ile (accessed [today's date]).

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