Is DOCK7 p.Arg231Ser (c.691C>A) pathogenic?

DOCK7 p.Arg231Ser (c.691C>A) is classified Uncertain significance in DOCK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-29). AlphaMissense: likely pathogenic (0.989); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DOCK7 p.Arg231Ser (c.691C>A)?

DOCK7 p.Arg231Ser (c.691C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK7 p.Arg231Ser (c.691C>A) in the general population?

DOCK7 p.Arg231Ser (c.691C>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about DOCK7 p.Arg231Ser (c.691C>A)?

AlphaMissense predicts likely pathogenic (score 0.989) — an in-silico prediction, not a clinical call.

DOCK7 p.Arg231Ser

c.691C>A · rs1254316274 · VCV2218562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.989 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.989	likely pathogenic · top 10% in DOCK7
REVEL	0.294	indeterminate
SaProt	LLR -5.64	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 175 kb · p 3.6e-10 · regional, not allelic
Overall
CADD	26.5	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 0.000424% European (non-Finnish) · 5/1,179,602 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,288 alleles · very rare exomes 5/1,461,244 · genomes 0/152,044 · joint denominator

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: DOCK7
Protein: p.Arg231Ser
Coding: c.691C>A
MANE Select: NM_001367561
dbSNP: rs1254316274
Type: single nucleotide variant
Location: chr1:62648147 (GRCh38)
Gene constraint: LOEUF 0.551 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 2 PDB

Full DOCK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK7 p.Arg231His Uncertain significance ★★ ⚠ same residue
DOCK7 p.Arg231Cys Uncertain significance ★★ ⚠ same residue
DOCK7 p.Arg231Gly Uncertain significance ★★ ⚠ same residue
DOCK7 c.3781+4C>G Uncertain significance ★★ same condition
DOCK7 p.Ala1479Thr Uncertain significance ★★ ⚠ same condition
DOCK7 p.Ala205Thr Uncertain significance ★★ ⚠ same condition
DOCK7 p.Arg1266Gln Uncertain significance ★★ ⚠ same condition
DOCK7 p.Arg1358Gln Uncertain significance ★★ ⚠ 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/dock7-p-arg231ser (accessed [today's date]).

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