Is ANKRD11 p.Pro2191Ser (c.6571C>T) pathogenic?

ANKRD11 p.Pro2191Ser (c.6571C>T) is classified Conflicting classifications of pathogenicity in ANKRD11 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-03-13). AlphaMissense: likely benign (0.0991); Ultra-rare (popmax 0.0417%, amr); Associated with KBG syndrome.

What condition is associated with ANKRD11 p.Pro2191Ser (c.6571C>T)?

ANKRD11 p.Pro2191Ser (c.6571C>T) is associated with KBG syndrome (ClinVar).

How common is ANKRD11 p.Pro2191Ser (c.6571C>T) in the general population?

ANKRD11 p.Pro2191Ser (c.6571C>T) is ultra-rare (popmax 0.0417%, amr) (gnomAD).

What do computational predictors say about ANKRD11 p.Pro2191Ser (c.6571C>T)?

AlphaMissense predicts likely benign (score 0.0991) — an in-silico prediction, not a clinical call.

ANKRD11 p.Pro2191Ser

c.6571C>T · rs757615498 · VCV836606

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0991 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

KBG syndrome

Computational evidence

Protein change
AlphaMissense	0.0991	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.31	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 2.6	GERP -2.6, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 5,665 bp · p 6.8e-35 · regional, not allelic
Overall
CADD	10.47	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 0.0417% Admixed American · 25/60,000 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00366% 59/1,610,602 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0417%	2,400
Middle Eastern	0.0165%	6,052
Remaining individualsnot grpmax-eligible	0.0048%	20,812
European (non-Finnish)	0.00254%	39,330

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.Pro2191Ser
Coding: c.6571C>T
MANE Select: NM_013275
dbSNP: rs757615498
Type: single nucleotide variant
Location: chr16:89279971 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.44
Residue 2191: the 'disordered' region

Full ANKRD11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KBG syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANKRD11 p.Pro2191= 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-pro2191ser (accessed [today's date]).

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