Is BLMH p.Asp129Asn (c.385G>A) pathogenic?

BLMH p.Asp129Asn (c.385G>A) is classified Uncertain significance in BLMH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-27). AlphaMissense: likely benign (0.1209); Very rare (popmax 0.00167%, amr).

How common is BLMH p.Asp129Asn (c.385G>A) in the general population?

BLMH p.Asp129Asn (c.385G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BLMH p.Asp129Asn (c.385G>A)?

AlphaMissense predicts likely benign (score 0.1209) — an in-silico prediction, not a clinical call.

BLMH p.Asp129Asn

c.385G>A · VCV3991702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1209 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1209	likely benign
REVEL	0.29	benign-leaning
SaProt	LLR -8.97	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 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.36	unconstrained · MANE · 93 bp · p 8e-05 · regional, not allelic
Overall
CADD	26.0	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 0.00167% Admixed American · 1/60,030 alleles

Overall 0.000656% 1/152,332 alleles · very rare

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.Asp129Asn
Coding: c.385G>A
MANE Select: NM_000386
Type: single nucleotide variant
Location: chr17:30287884 (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-asp129asn (accessed [today's date]).

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