Is DOCK10 p.Ser548Arg (c.1644C>A) pathogenic?

DOCK10 p.Ser548Arg (c.1644C>A) is classified Uncertain significance in DOCK10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely pathogenic (0.8072); Ultra-rare (popmax 0.0199%, sas).

How common is DOCK10 p.Ser548Arg (c.1644C>A) in the general population?

DOCK10 p.Ser548Arg (c.1644C>A) is ultra-rare (popmax 0.0199%, sas) (gnomAD).

What do computational predictors say about DOCK10 p.Ser548Arg (c.1644C>A)?

AlphaMissense predicts likely pathogenic (score 0.8072) — an in-silico prediction, not a clinical call.

DOCK10 p.Ser548Arg

c.1644C>A · VCV4661636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8072 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0199%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8072	likely pathogenic
REVEL	0.229	benign-leaning
SaProt	LLR -5.00	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.95, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 219 kb · p 0.24 · regional, not allelic
Overall
CADD	23.7	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 0.0199% South Asian · 18/90,448 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00192% 28/1,459,296 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0199%	5,025
Middle Eastern	0.0165%	6,054
Remaining individualsnot grpmax-eligible	0.0016%	62,382
European (non-Finnish)	0.000679%	147,344

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: DOCK10
Protein: p.Ser548Arg
Coding: c.1644C>A
MANE Select: NM_014689
Type: single nucleotide variant
Location: chr2:224862705 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.47 · 4 PDB

Full DOCK10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK10 p.Ser548Gly Likely benign ★ same residue
DOCK10 p.Asp2034= Benign ★★ same type
DOCK10 p.Ser1349= Benign ★★ same type
DOCK10 p.Thr1950= Benign ★★ same type
DOCK10 p.Ala112Ser Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1135Thr Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1175Thr Uncertain significance ★ ⚠ same type
DOCK10 p.Ala1177Ser 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/dock10-p-ser548arg (accessed [today's date]).

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