Is BLMH p.Ala314Val (c.941C>T) pathogenic?

BLMH p.Ala314Val (c.941C>T) is classified Uncertain significance in BLMH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely benign (0.1113); Ultra-rare (popmax 0.0746%, afr).

How common is BLMH p.Ala314Val (c.941C>T) in the general population?

BLMH p.Ala314Val (c.941C>T) is ultra-rare (popmax 0.0746%, afr) (gnomAD).

What do computational predictors say about BLMH p.Ala314Val (c.941C>T)?

AlphaMissense predicts likely benign (score 0.1113) — an in-silico prediction, not a clinical call.

BLMH p.Ala314Val

c.941C>T · rs372310785 · VCV2379208

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1113 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0746%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1113	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -9.25	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 10	GERP 6.3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 39 kb · p 0.0015 · regional, not allelic
Overall
CADD	22.7	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 0.0746% African / African-American · 56/75,020 alleles

Filtering AF 0.059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0533%

Overall 0.00409% 66/1,614,138 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0746%	1,340
Middle Eastern	0.0165%	6,062
Admixed American	0.00833%	12,002
Remaining individualsnot grpmax-eligible	0.0048%	20,837
South Asian	0.0011%	91,078

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.Ala314Val
Coding: c.941C>T
MANE Select: NM_000386
dbSNP: rs372310785
Type: single nucleotide variant
Location: chr17:30272760 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 98.10 · 6 PDB
Residue 314: an α-helix

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

Similar variants

BLMH p.Ala314Ser Uncertain significance ★ ⚠ same residue
BLMH p.Ala117Gly Uncertain significance ★ ⚠ same type
BLMH p.Ala13Val Uncertain significance ★ ⚠ same type
BLMH p.Ala313Val 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
BLMH p.Asn241Ile 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-ala314val (accessed [today's date]).

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