Is ANKRD11 p.Ala94Pro (c.280G>C) pathogenic?

ANKRD11 p.Ala94Pro (c.280G>C) is classified Benign/Likely benign in ANKRD11 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-10-15). AlphaMissense: likely benign (0.1502); Rare (popmax 0.508%, eas); Associated with Inborn genetic diseases.

What condition is associated with ANKRD11 p.Ala94Pro (c.280G>C)?

ANKRD11 p.Ala94Pro (c.280G>C) is associated with Inborn genetic diseases, KBG syndrome (ClinVar).

How common is ANKRD11 p.Ala94Pro (c.280G>C) in the general population?

ANKRD11 p.Ala94Pro (c.280G>C) is rare (popmax 0.508%, eas) (gnomAD).

What do computational predictors say about ANKRD11 p.Ala94Pro (c.280G>C)?

AlphaMissense predicts likely benign (score 0.1502) — an in-silico prediction, not a clinical call.

ANKRD11 p.Ala94Pro

c.280G>C · rs190143218 · VCV587941

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1502 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.508%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1502	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -5.48	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 2.1	GERP -3.7, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 26 kb · p 0.0051 · regional, not allelic
Overall
CADD	17.25	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 0.508% East Asian · 228/44,878 alleles

Filtering AF 0.454% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.433%

Overall 0.0189% 305/1,613,990 alleles · rare exomes 255/1,461,712 · genomes 50/152,278 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.508%	197
South Asian	0.0637%	1,570
Middle Eastern	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.0272%	3,676

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: ANKRD11
Protein: p.Ala94Pro
Coding: c.280G>C
MANE Select: NM_013275
dbSNP: rs190143218
Type: single nucleotide variant
Location: chr16:89291130 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.44

Full ANKRD11 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

Also linked: KBG syndrome

Similar variants

ANKRD11 p.Ala94= Likely benign ★ same residue
ANKRD11 c.744+1G>T Pathogenic ★★ same condition
ANKRD11 c.745-2A>G Likely pathogenic ★★ same condition
ANKRD11 c.7470+1G>C Pathogenic ★★ same condition
ANKRD11 c.7569+1G>A Pathogenic ★★ same condition
ANKRD11 c.7569+1G>C Likely pathogenic ★★ same condition
ANKRD11 c.7570-1G>A Pathogenic ★★ same condition
ANKRD11 c.892+1G>A 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/ankrd11-p-ala94pro (accessed [today's date]).

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