Is DOK7 p.Ser315Ter (c.944C>G) pathogenic?

DOK7 p.Ser315Ter (c.944C>G) is classified Likely pathogenic in DOK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-10). Very rare (popmax 0.00272%, afr); Associated with fetal akinesia deformation sequence 3.

What condition is associated with DOK7 p.Ser315Ter (c.944C>G)?

DOK7 p.Ser315Ter (c.944C>G) is associated with fetal akinesia deformation sequence 3 (ClinVar).

How common is DOK7 p.Ser315Ter (c.944C>G) in the general population?

DOK7 p.Ser315Ter (c.944C>G) is very rare (popmax 0.00272%, afr) (gnomAD).

DOK7 p.Ser315Ter

c.944C>G · rs898501852 · VCV2674900

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00272%, afr)

Conditions

fetal akinesia deformation sequence 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -0.022, phastCons 0.005
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00272% African / African-American · 2/73,640 alleles

Filtering AF 0.000451% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000169%

Overall 0.00197% 3/152,204 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00272%	36,820
European (non-Finnish)	8.65e-05%	1,155,682

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: DOK7
Protein: p.Ser315Ter
Coding: c.944C>G
MANE Select: NM_173660
dbSNP: rs898501852
Type: single nucleotide variant
Location: chr4:3492930 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 315: the 'disordered' region

Full DOK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

fetal akinesia deformation sequence 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOK7 p.Ser315= Likely benign ★ same residue
DOK7 c.331+1G>T Pathogenic ★★ same condition
DOK7 c.332-1G>A Likely pathogenic ★★ same condition
DOK7 c.332-1G>C Likely pathogenic ★★ same condition
DOK7 p.Arg201Ter Pathogenic ★★ same condition
DOK7 p.Cys412Ter Pathogenic ★★ same condition
DOK7 p.Gln151Ter Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Gln296Ter Likely pathogenic ★★ same condition

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/dok7-p-ser315ter (accessed [today's date]).

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