Is DNAJB5 p.Pro271Ser (c.811C>T) pathogenic?

DNAJB5 p.Pro271Ser (c.811C>T) is classified Uncertain significance in DNAJB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely benign (0.0956); Very rare (popmax 0.0011%, sas).

How common is DNAJB5 p.Pro271Ser (c.811C>T) in the general population?

DNAJB5 p.Pro271Ser (c.811C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DNAJB5 p.Pro271Ser (c.811C>T)?

AlphaMissense predicts likely benign (score 0.0956) — an in-silico prediction, not a clinical call.

DNAJB5 p.Pro271Ser

c.811C>T · VCV4661286

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0956 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0956	likely benign
REVEL	0.434	indeterminate
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.75, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 3,966 bp · p 2.3e-20 · regional, not allelic
Overall
CADD	23.1	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P199S vs ClinVar P271S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,086 alleles

Overall 6.84e-05% 1/1,461,862 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: DNAJB5
Protein: p.Pro271Ser
Coding: c.811C>T
MANE Select: NM_001349723
Type: single nucleotide variant
Location: chr9:34996648 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 80.69

Full DNAJB5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB5 p.Arg277His Uncertain significance ★★ ⚠ same type
DNAJB5 p.Glu141= Uncertain significance ★★ same type
DNAJB5 p.Thr406Pro Uncertain significance ★★ ⚠ same type
DNAJB5 c.40G>A Uncertain significance ★ same type
DNAJB5 c.50T>C Uncertain significance ★ same type
DNAJB5 c.55G>C Uncertain significance ★ same type
DNAJB5 c.58C>T Uncertain significance ★ same type
DNAJB5 c.-133+6G>A 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/dnajb5-p-pro271ser (accessed [today's date]).

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