Is DNAJB7 p.Arg277Ser (c.831A>T) pathogenic?

DNAJB7 p.Arg277Ser (c.831A>T) is classified Uncertain significance in DNAJB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely benign (0.162); Very rare (popmax 0.000254%, nfe).

How common is DNAJB7 p.Arg277Ser (c.831A>T) in the general population?

DNAJB7 p.Arg277Ser (c.831A>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about DNAJB7 p.Arg277Ser (c.831A>T)?

AlphaMissense predicts likely benign (score 0.162) — an in-silico prediction, not a clinical call.

DNAJB7 p.Arg277Ser

c.831A>T · VCV3841463

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.162 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.162	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -4.79	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 2.7	GERP 0.95, phastCons 0.33
Regional constraint	o/e 1.17	unconstrained · MANE · 926 bp · p 0.0012 · regional, not allelic
Overall
CADD	10.3	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 0.000254% European (non-Finnish) · 3/1,180,030 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,046 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: DNAJB7
Protein: p.Arg277Ser
Coding: c.831A>T
MANE Select: NM_145174
Type: single nucleotide variant
Location: chr22:40861164 (GRCh38)
Gene constraint: LOEUF 1.85 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 59.38

Full DNAJB7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB7 p.Ala27Thr Uncertain significance ★ ⚠ same type
DNAJB7 p.Ala50Gly Uncertain significance ★ ⚠ same type
DNAJB7 p.Arg122Gly Uncertain significance ★ ⚠ same type
DNAJB7 p.Arg12Lys Uncertain significance ★ ⚠ same type
DNAJB7 p.Arg307Lys Uncertain significance ★ ⚠ same type
DNAJB7 p.Arg62Gln Uncertain significance ★ ⚠ same type
DNAJB7 p.Asn200Lys Uncertain significance ★ ⚠ same type
DNAJB7 p.Asn38Lys 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/dnajb7-p-arg277ser (accessed [today's date]).

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