Is DNAJC14 p.Asn660Ser (c.1979A>G) pathogenic?

DNAJC14 p.Asn660Ser (c.1979A>G) is classified Uncertain significance in DNAJC14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.0576); Ultra-rare (popmax 0.0244%, nfe).

How common is DNAJC14 p.Asn660Ser (c.1979A>G) in the general population?

DNAJC14 p.Asn660Ser (c.1979A>G) is ultra-rare (popmax 0.0244%, nfe) (gnomAD).

What do computational predictors say about DNAJC14 p.Asn660Ser (c.1979A>G)?

AlphaMissense predicts likely benign (score 0.0576) — an in-silico prediction, not a clinical call.

DNAJC14 p.Asn660Ser

c.1979A>G · rs199633418 · VCV2507701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0576 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0244%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0576	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -4.97	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 6.1	GERP 1.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 651 bp · p 0.026 · regional, not allelic
Overall
CADD	19.52	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 0.0244% European (non-Finnish) · 288/1,179,870 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0212%

Overall 0.0195% 314/1,613,756 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0244%	4,097
Remaining individualsnot grpmax-eligible	0.0192%	5,208
African / African-American	0.008%	12,501
East Asian	0.00668%	14,961
Admixed American	0.00334%	29,971
South Asian	0.0033%	30,342

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.Asn660Ser
Coding: c.1979A>G
MANE Select: NM_032364
dbSNP: rs199633418
Type: single nucleotide variant
Location: chr12:55822107 (GRCh38)
Gene constraint: LOEUF 0.272 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.30
Residue 660: the 'disordered' region

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

Similar variants

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
DNAJC14 p.Ala302Thr 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-asn660ser (accessed [today's date]).

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