Is DNAJB6 p.Phe164Ser (c.491T>C) pathogenic?

DNAJB6 p.Phe164Ser (c.491T>C) is classified Uncertain significance in DNAJB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-17). AlphaMissense: likely pathogenic (0.7195); Absent from gnomAD v4.1; Associated with autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6).

What condition is associated with DNAJB6 p.Phe164Ser (c.491T>C)?

DNAJB6 p.Phe164Ser (c.491T>C) is associated with autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) (ClinVar).

How common is DNAJB6 p.Phe164Ser (c.491T>C) in the general population?

DNAJB6 p.Phe164Ser (c.491T>C) is absent from gnomAD v4.1 (gnomAD).

How is DNAJB6-related limb-girdle muscular dystrophy D1 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DNAJB6 p.Phe164Ser (c.491T>C)?

AlphaMissense predicts likely pathogenic (score 0.7195) — an in-silico prediction, not a clinical call.

DNAJB6 p.Phe164Ser

c.491T>C · VCV3662713

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7195 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.7195	likely pathogenic
REVEL	0.453	indeterminate
SaProt	LLR -9.07	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 49 kb · p 0.16 · regional, not allelic
Overall
CADD	24.9	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: DNAJB6
Protein: p.Phe164Ser
Coding: c.491T>C
MANE Select: NM_058246
Type: single nucleotide variant
Location: chr7:157384879 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.04 · 4 PDB
Residue 164: the 'interaction with krt18' region

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

Disease context

autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For DNAJB6-related limb-girdle muscular dystrophy D1 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

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
DNAJB6 p.Ala237Pro 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-phe164ser (accessed [today's date]).

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