Is DNAJC27 p.Phe129Ser (c.386T>C) pathogenic?

DNAJC27 p.Phe129Ser (c.386T>C) is classified Uncertain significance in DNAJC27 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely pathogenic (0.8305); Very rare (popmax 0.00102%, nfe).

How common is DNAJC27 p.Phe129Ser (c.386T>C) in the general population?

DNAJC27 p.Phe129Ser (c.386T>C) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about DNAJC27 p.Phe129Ser (c.386T>C)?

AlphaMissense predicts likely pathogenic (score 0.8305) — an in-silico prediction, not a clinical call.

DNAJC27 p.Phe129Ser

c.386T>C · rs1487353843 · VCV3084563

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8305 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8305	likely pathogenic
REVEL	0.708	pathogenic-leaning
SaProt	LLR -9.78	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic
Overall
CADD	28.6	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 0.00102% European (non-Finnish) · 12/1,179,972 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000821% 12/1,461,794 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: DNAJC27
Protein: p.Phe129Ser
Coding: c.386T>C
MANE Select: NM_016544
dbSNP: rs1487353843
Type: single nucleotide variant
Location: chr2:24957829 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 90.75 · 1 PDB

Full DNAJC27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC27 p.Ala106Val Uncertain significance ★ ⚠ same type
DNAJC27 p.Ala236Val Uncertain significance ★ ⚠ same type
DNAJC27 p.Ala264Val Uncertain significance ★ ⚠ same type
DNAJC27 p.Ala73Val Uncertain significance ★ ⚠ same type
DNAJC27 p.Arg142His Uncertain significance ★ ⚠ same type
DNAJC27 p.Arg150Cys Uncertain significance ★ ⚠ same type
DNAJC27 p.Arg192His Uncertain significance ★ ⚠ same type
DNAJC27 p.Arg210Cys 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/dnajc27-p-phe129ser (accessed [today's date]).

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