Is BLMH p.Arg43Trp (c.127C>T) pathogenic?

BLMH p.Arg43Trp (c.127C>T) is classified Uncertain significance in BLMH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-22). AlphaMissense: ambiguous (0.4662); Absent from gnomAD v4.1.

How common is BLMH p.Arg43Trp (c.127C>T) in the general population?

BLMH p.Arg43Trp (c.127C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BLMH p.Arg43Trp (c.127C>T)?

AlphaMissense predicts ambiguous (score 0.4662) — an in-silico prediction, not a clinical call.

BLMH p.Arg43Trp

c.127C>T · rs1597670127 · VCV2273608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4662 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4662	ambiguous
REVEL	0.426	indeterminate
SaProt	LLR -12.02	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 0.41, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 493 bp · p 0.87 · regional, not allelic
Overall
CADD	25.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BLMH
Protein: p.Arg43Trp
Coding: c.127C>T
MANE Select: NM_000386
dbSNP: rs1597670127
Type: single nucleotide variant
Location: chr17:30291395 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 98.10 · 6 PDB
Residue 43: 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.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-arg43trp (accessed [today's date]).

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