Is DNAJC14 p.Arg376Pro (c.1127G>C) pathogenic?

DNAJC14 p.Arg376Pro (c.1127G>C) is classified Uncertain significance in DNAJC14 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-29). AlphaMissense: likely benign (0.2378); Very rare (popmax 0.00167%, amr).

How common is DNAJC14 p.Arg376Pro (c.1127G>C) in the general population?

DNAJC14 p.Arg376Pro (c.1127G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DNAJC14 p.Arg376Pro (c.1127G>C)?

AlphaMissense predicts likely benign (score 0.2378) — an in-silico prediction, not a clinical call.

DNAJC14 p.Arg376Pro

c.1127G>C · rs201520030 · VCV3084484

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2378 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2378	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -9.05	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 -3.3	GERP -3.4
Regional constraint	o/e 0.99	unconstrained · MANE · 1,273 bp · p 0.74 · regional, not allelic
Overall
CADD	10.35	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 0.00167% Admixed American · 1/59,830 alleles

Filtering AF 0.000503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000368%

Overall 0.000747% 12/1,605,626 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,830
European (non-Finnish)	0.000938%	106,631

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: DNAJC14
Protein: p.Arg376Pro
Coding: c.1127G>C
MANE Select: NM_032364
dbSNP: rs201520030
Type: single nucleotide variant
Location: chr12:55827532 (GRCh38)
Gene constraint: LOEUF 0.272 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.30

Full DNAJC14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC14 p.Arg376Cys Uncertain significance ★ ⚠ same residue
DNAJC14 p.Arg389Gln Likely benign ★★ same type
DNAJC14 p.Ala128Val Uncertain significance ★ ⚠ same type
DNAJC14 p.Ala161Thr Uncertain significance ★ ⚠ same type
DNAJC14 p.Ala20Gly Uncertain significance ★ ⚠ same type
DNAJC14 p.Ala20Val Uncertain significance ★ ⚠ same type
DNAJC14 p.Ala250Glu Uncertain significance ★ ⚠ same type
DNAJC14 p.Ala275Ser 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/dnajc14-p-arg376pro (accessed [today's date]).

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