Is ANKRD11 p.Pro16Ser (c.46C>T) pathogenic?

ANKRD11 p.Pro16Ser (c.46C>T) is classified Uncertain significance in ANKRD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). AlphaMissense: likely benign (0.0706); Absent from gnomAD v4.1; Associated with KBG syndrome.

What condition is associated with ANKRD11 p.Pro16Ser (c.46C>T)?

ANKRD11 p.Pro16Ser (c.46C>T) is associated with KBG syndrome (ClinVar).

How common is ANKRD11 p.Pro16Ser (c.46C>T) in the general population?

ANKRD11 p.Pro16Ser (c.46C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD11 p.Pro16Ser (c.46C>T)?

AlphaMissense predicts likely benign (score 0.0706) — an in-silico prediction, not a clinical call.

ANKRD11 p.Pro16Ser

c.46C>T · rs2544550694 · VCV3010352

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0706 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

KBG syndrome

Computational evidence

Protein change
AlphaMissense	0.0706	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -5.64	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 -0.81	GERP -3.4
Regional constraint	o/e 0.80	unconstrained · MANE · 26 kb · p 0.0051 · regional, not allelic
Overall
CADD	0.301	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANKRD11
Protein: p.Pro16Ser
Coding: c.46C>T
MANE Select: NM_013275
dbSNP: rs2544550694
Type: single nucleotide variant
Location: chr16:89316974 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.44
Residue 16: 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 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
ANKRD11 p.Arg1007Ter 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-pro16ser (accessed [today's date]).

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