Is ANKRD11 p.Pro334= (c.1002A>G) pathogenic?

ANKRD11 p.Pro334= (c.1002A>G) is classified Likely benign in ANKRD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). Very rare (popmax 0.00134%, afr); Associated with KBG syndrome.

What condition is associated with ANKRD11 p.Pro334= (c.1002A>G)?

ANKRD11 p.Pro334= (c.1002A>G) is associated with KBG syndrome (ClinVar).

How common is ANKRD11 p.Pro334= (c.1002A>G) in the general population?

ANKRD11 p.Pro334= (c.1002A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

ANKRD11 p.Pro334=

c.1002A>G · rs767149122 · VCV2911584

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

KBG syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.3	GERP -3.5
Overall
CADD	1.665	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,902 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.00062% 10/1,613,964 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,902
European (non-Finnish)	0.000763%	131,108

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.Pro334=
Coding: c.1002A>G
MANE Select: NM_013275
dbSNP: rs767149122
Type: single nucleotide variant
Location: chr16:89285540 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.44
Residue 334: 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.Pro334Arg Uncertain significance ★ ⚠ same residue
ANKRD11 p.Pro334Ser Uncertain significance ★ ⚠ 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-pro334 (accessed [today's date]).

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