Is ANKRD11 p.Pro359Ser (c.1075C>T) pathogenic?

ANKRD11 p.Pro359Ser (c.1075C>T) is classified Uncertain significance in ANKRD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-24). AlphaMissense: likely pathogenic (0.967); Absent from gnomAD v4.1; Associated with KBG syndrome.

What condition is associated with ANKRD11 p.Pro359Ser (c.1075C>T)?

ANKRD11 p.Pro359Ser (c.1075C>T) is associated with KBG syndrome (ClinVar).

How common is ANKRD11 p.Pro359Ser (c.1075C>T) in the general population?

ANKRD11 p.Pro359Ser (c.1075C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD11 p.Pro359Ser (c.1075C>T)?

AlphaMissense predicts likely pathogenic (score 0.967) — an in-silico prediction, not a clinical call.

ANKRD11 p.Pro359Ser

c.1075C>T · VCV3901028

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.967 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

KBG syndrome

Computational evidence

Protein change
AlphaMissense	0.967	likely pathogenic · top 9% in ANKRD11
REVEL	0.197	benign-leaning
SaProt	LLR -5.23	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 0.6, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 837 bp · p 0.0096 · regional, not allelic
Overall
CADD	24.8	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

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.Pro359Ser
Coding: c.1075C>T
MANE Select: NM_013275
Type: single nucleotide variant
Location: chr16:89285467 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.44
Residue 359: 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-pro359ser (accessed [today's date]).

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