Is ANKRD11 p.Arg2452Pro (c.7355G>C) pathogenic?

ANKRD11 p.Arg2452Pro (c.7355G>C) is classified Likely pathogenic in ANKRD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-23). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1; Associated with KBG syndrome.

What condition is associated with ANKRD11 p.Arg2452Pro (c.7355G>C)?

ANKRD11 p.Arg2452Pro (c.7355G>C) is associated with KBG syndrome (ClinVar).

How common is ANKRD11 p.Arg2452Pro (c.7355G>C) in the general population?

ANKRD11 p.Arg2452Pro (c.7355G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD11 p.Arg2452Pro (c.7355G>C)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

ANKRD11 p.Arg2452Pro

c.7355G>C · rs781584370 · VCV1698849

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

KBG syndrome

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic ✓ concordant with ClinVar · top 1% in ANKRD11
REVEL	0.565	indeterminate
SaProt	LLR -11.75	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 11 kb · p 2.8e-35 · regional, not allelic
Overall
CADD	25.0	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.Arg2452Pro
Coding: c.7355G>C
MANE Select: NM_013275
dbSNP: rs781584370
Type: single nucleotide variant
Location: chr16:89279187 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.44
Residue 2452: the 'important for protein degradation' 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.Arg2452Gly Pathogenic/Likely pathogenic ★★ ⚠ same residue
ANKRD11 p.Arg2452Cys Likely pathogenic ★ ⚠ 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

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-arg2452pro (accessed [today's date]).

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