Is DOCK7 p.Met181Val (c.541A>G) pathogenic?

DOCK7 p.Met181Val (c.541A>G) is classified Benign in DOCK7 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0718); Common (popmax 12.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with developmental and epileptic encephalopathy, 23.

What condition is associated with DOCK7 p.Met181Val (c.541A>G)?

DOCK7 p.Met181Val (c.541A>G) is associated with developmental and epileptic encephalopathy, 23 (ClinVar).

What do computational predictors say about DOCK7 p.Met181Val (c.541A>G)?

AlphaMissense predicts likely benign (score 0.0718) — an in-silico prediction, not a clinical call.

DOCK7 p.Met181Val

Q: How common is DOCK7 p.Met181Val (c.541A>G) in the general population?

DOCK7 p.Met181Val (c.541A>G) is common (popmax 12.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.541A>G · rs61743961 · VCV447277

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0718 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 12.1%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 23

Computational evidence

Protein change
AlphaMissense	0.0718	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -5.63	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 -0.98	GERP -5
Regional constraint	o/e 0.85	unconstrained · MANE · 175 kb · p 3.6e-10 · regional, not allelic
Overall
CADD	10.87	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 12.1% East Asian · 5,432/44,798 alleles

Filtering AF 11.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.7%

Overall 1.03% 16,676/1,611,734 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	12.1%	8
African / African-American	11.8%	9
Remaining individualsnot grpmax-eligible	1.35%	74
Admixed American	0.76%	131
South Asian	0.532%	188
Middle Eastern	0.314%	319
Ashkenazi Jewishnot grpmax-eligible	0.295%	339
European (non-Finnish)	0.0464%	2,155
Finnishnot grpmax-eligible	0.00626%	15,968

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.Met181Val
Coding: c.541A>G
MANE Select: NM_001367561
dbSNP: rs61743961
Type: single nucleotide variant
Location: chr1:62648297 (GRCh38)
Gene constraint: LOEUF 0.551 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 2 PDB
Residue 181: the 'disordered' region

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

Disease context

developmental and epileptic encephalopathy, 23 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK7 p.Met181Leu Uncertain significance ★ ⚠ same residue
DOCK7 c.4924-1G>A Pathogenic/Likely pathogenic ★★ same condition
DOCK7 p.Arg1380Ter Pathogenic ★★ same condition
DOCK7 p.Arg1415Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK7 p.Arg429Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK7 p.Arg445Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK7 c.3781+4C>G Uncertain significance ★★ same condition
DOCK7 c.38+6T>C 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-met181val (accessed [today's date]).

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