Is DNAJB6 p.Ala143Val (c.428C>T) pathogenic?

DNAJB6 p.Ala143Val (c.428C>T) is classified Conflicting classifications of pathogenicity in DNAJB6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-18). AlphaMissense: likely benign (0.2277); Ultra-rare (popmax 0.0331%, sas); Associated with Inborn genetic diseases.

What condition is associated with DNAJB6 p.Ala143Val (c.428C>T)?

DNAJB6 p.Ala143Val (c.428C>T) is associated with Inborn genetic diseases, autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) (ClinVar).

How common is DNAJB6 p.Ala143Val (c.428C>T) in the general population?

DNAJB6 p.Ala143Val (c.428C>T) is ultra-rare (popmax 0.0331%, sas) (gnomAD).

What do computational predictors say about DNAJB6 p.Ala143Val (c.428C>T)?

AlphaMissense predicts likely benign (score 0.2277) — an in-silico prediction, not a clinical call.

DNAJB6 p.Ala143Val

c.428C>T · rs757767434 · VCV283403

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2277 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2277	likely benign
REVEL	0.146	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 3.8	GERP 1.1, phastCons 0.2
Regional constraint	o/e 0.92	unconstrained · MANE · 49 kb · p 0.16 · regional, not allelic
Overall
CADD	19.22	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 0.0331% South Asian · 30/90,754 alleles

Filtering AF 0.0238% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0206%

Overall 0.00218% 35/1,604,720 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0331%	3,025
Remaining individualsnot grpmax-eligible	0.00323%	30,928
East Asian	0.00225%	44,352
European (non-Finnish)	0.00017%	588,111

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: DNAJB6
Protein: p.Ala143Val
Coding: c.428C>T
MANE Select: NM_058246
dbSNP: rs757767434
Type: single nucleotide variant
Location: chr7:157382327 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.04 · 4 PDB
Residue 143: the 'interaction with hsp70' region; the 'interaction with krt18' region

Full DNAJB6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)

Similar variants

DNAJB6 p.Ala143= Benign/Likely benign ★★ same residue
DNAJB6 p.Phe89Ile Pathogenic ★★ same condition
DNAJB6 p.Phe91Leu Pathogenic ★★ same condition
DNAJB6 p.Phe91Val Pathogenic/Likely pathogenic ★★ same condition
DNAJB6 p.Pro96Arg Pathogenic ★★ same condition
DNAJB6 c.66-2A>G Uncertain significance ★★ same condition
DNAJB6 c.-7G>A Uncertain significance ★★ same condition
DNAJB6 p.Ala22Val Uncertain significance ★★ ⚠ same condition

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/dnajb6-p-ala143val (accessed [today's date]).

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