Is ANKRD11 p.Ser747Pro (c.2239T>C) pathogenic?

ANKRD11 p.Ser747Pro (c.2239T>C) is classified Likely benign in ANKRD11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.0712); Ultra-rare (popmax 0.0201%, afr); Associated with Inborn genetic diseases.

What condition is associated with ANKRD11 p.Ser747Pro (c.2239T>C)?

ANKRD11 p.Ser747Pro (c.2239T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ANKRD11 p.Ser747Pro (c.2239T>C) in the general population?

ANKRD11 p.Ser747Pro (c.2239T>C) is ultra-rare (popmax 0.0201%, afr) (gnomAD).

What do computational predictors say about ANKRD11 p.Ser747Pro (c.2239T>C)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

ANKRD11 p.Ser747Pro

c.2239T>C · rs142059753 · VCV1326138

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -7.94	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	GERP -3.3
Regional constraint	o/e 1.25	unconstrained · MANE · 5,665 bp · p 6.8e-35 · regional, not allelic
Overall
CADD	0.004	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 0.0201% African / African-American · 15/74,512 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00994%

Overall 0.000992% 16/1,612,816 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0201%	4,967
European (non-Finnish)	8.48e-05%	1,179,901

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.Ser747Pro
Coding: c.2239T>C
MANE Select: NM_013275
dbSNP: rs142059753
Type: single nucleotide variant
Location: chr16:89284303 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.44
Residue 747: the 'disordered' region

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

Similar variants

ANKRD11 p.Ser747Leu Benign/Likely benign ★★ same residue
ANKRD11 c.744+1G>T Pathogenic ★★ same condition
ANKRD11 c.7569+1G>A Pathogenic ★★ same condition
ANKRD11 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
ANKRD11 p.Arg2512Gln Pathogenic/Likely pathogenic ★★ same condition
ANKRD11 p.Arg2536Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
ANKRD11 p.Arg54Ter Pathogenic ★★ same condition
ANKRD11 p.Arg733Ter Pathogenic/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-ser747pro (accessed [today's date]).

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