Is BLMH p.Phe332Val (c.994T>G) pathogenic?

BLMH p.Phe332Val (c.994T>G) is classified Uncertain significance in BLMH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: ambiguous (0.5286); Ultra-rare (popmax 0.035%, amr).

How common is BLMH p.Phe332Val (c.994T>G) in the general population?

BLMH p.Phe332Val (c.994T>G) is ultra-rare (popmax 0.035%, amr) (gnomAD).

What do computational predictors say about BLMH p.Phe332Val (c.994T>G)?

AlphaMissense predicts ambiguous (score 0.5286) — an in-silico prediction, not a clinical call.

BLMH p.Phe332Val

c.994T>G · rs754513319 · VCV2371948

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5286 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Computational evidence

Protein change
AlphaMissense	0.5286	ambiguous
REVEL	0.496	indeterminate
SaProt	LLR -8.28	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 4.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 39 kb · p 0.0015 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.035% Admixed American · 21/60,026 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00157% 23/1,461,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,858
Remaining individualsnot grpmax-eligible	0.0032%	31,253

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.Phe332Val
Coding: c.994T>G
MANE Select: NM_000386
dbSNP: rs754513319
Type: single nucleotide variant
Location: chr17:30272595 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 98.10 · 6 PDB

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-phe332val (accessed [today's date]).

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