Is DNAJC14 p.Thr207Ser (c.620C>G) pathogenic?

DNAJC14 p.Thr207Ser (c.620C>G) is classified Uncertain significance in DNAJC14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.0789); Rare (popmax 0.116%, mid).

How common is DNAJC14 p.Thr207Ser (c.620C>G) in the general population?

DNAJC14 p.Thr207Ser (c.620C>G) is rare (popmax 0.116%, mid) (gnomAD).

What do computational predictors say about DNAJC14 p.Thr207Ser (c.620C>G)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

DNAJC14 p.Thr207Ser

c.620C>G · rs187204947 · VCV2464484

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -5.15	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 1.9	GERP -2.9, phastCons 0.62
Regional constraint	o/e 0.99	unconstrained · MANE · 1,273 bp · p 0.74 · regional, not allelic
Overall
CADD	4.062	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 0.116% Middle Eastern · 7/6,060 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.0036% 58/1,613,178 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.116%	866
African / African-American	0.0293%	3,410
Remaining individualsnot grpmax-eligible	0.016%	6,246
Admixed American	0.00668%	14,971
South Asian	0.0022%	45,494
European (non-Finnish)	0.0011%	90,742

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.Thr207Ser
Coding: c.620C>G
MANE Select: NM_032364
dbSNP: rs187204947
Type: single nucleotide variant
Location: chr12:55828039 (GRCh38)
Gene constraint: LOEUF 0.272 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.30
Residue 207: 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-thr207ser (accessed [today's date]).

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