Is ANKRD10 p.Ser2Trp (c.5C>G) pathogenic?

ANKRD10 p.Ser2Trp (c.5C>G) is classified Uncertain significance in ANKRD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: ambiguous (0.3939); Rare (popmax 0.159%, mid).

How common is ANKRD10 p.Ser2Trp (c.5C>G) in the general population?

ANKRD10 p.Ser2Trp (c.5C>G) is rare (popmax 0.159%, mid) (gnomAD).

What do computational predictors say about ANKRD10 p.Ser2Trp (c.5C>G)?

AlphaMissense predicts ambiguous (score 0.3939) — an in-silico prediction, not a clinical call.

ANKRD10 p.Ser2Trp

c.5C>G · rs867894429 · VCV3122069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3939 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.159%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3939	ambiguous
REVEL	0.224	benign-leaning
SaProt	LLR -8.82	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 0.79, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 35 kb · p 0.029 · regional, not allelic
Overall
CADD	25.0	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 0.159% Middle Eastern · 7/4,392 alleles

Filtering AF 0.0747% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0531%

Overall 0.00528% 81/1,532,748 alleles · rare exomes 75/1,380,496 · genomes 6/152,252 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.159%	627
South Asian	0.012%	8,347
Remaining individualsnot grpmax-eligible	0.0101%	9,942
European (non-Finnish)	0.00472%	21,201
Admixed American	0.00393%	25,423
African / African-American	0.00275%	36,394

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: ANKRD10
Protein: p.Ser2Trp
Coding: c.5C>G
MANE Select: NM_017664
dbSNP: rs867894429
Type: single nucleotide variant
Location: chr13:110914930 (GRCh38)
Gene constraint: LOEUF 1.035 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.99

Full ANKRD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD10 p.Ala237Val Uncertain significance ★ ⚠ same type
ANKRD10 p.Ala359Thr Uncertain significance ★ ⚠ same type
ANKRD10 p.Ala99Val Uncertain significance ★ ⚠ same type
ANKRD10 p.Asn186Lys Uncertain significance ★ ⚠ same type
ANKRD10 p.Gln106Arg Uncertain significance ★ ⚠ same type
ANKRD10 p.Gln113Glu Uncertain significance ★ ⚠ same type
ANKRD10 p.Gln171Arg Uncertain significance ★ ⚠ same type
ANKRD10 p.Gln199Glu 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/ankrd10-p-ser2trp (accessed [today's date]).

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