Is ANKRD11 p.Pro1643= (c.4929G>A) pathogenic?

ANKRD11 p.Pro1643= (c.4929G>A) is classified Benign/Likely benign in ANKRD11 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-10). Ultra-rare (popmax 0.04%, amr); Associated with KBG syndrome.

What condition is associated with ANKRD11 p.Pro1643= (c.4929G>A)?

ANKRD11 p.Pro1643= (c.4929G>A) is associated with KBG syndrome (ClinVar).

How common is ANKRD11 p.Pro1643= (c.4929G>A) in the general population?

ANKRD11 p.Pro1643= (c.4929G>A) is ultra-rare (popmax 0.04%, amr) (gnomAD).

ANKRD11 p.Pro1643=

c.4929G>A · rs142939070 · VCV1198023

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, amr)

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 -0.55	GERP -2.6
Overall
CADD	2.268	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.04% Admixed American · 24/60,006 alleles

Filtering AF 0.0276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0234%

Overall 0.00725% 117/1,614,046 alleles · ultra-rare exomes 104/1,461,888 · genomes 13/152,158 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.04%	2,500
European (non-Finnish)	0.00754%	13,259
South Asian	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Pro1643=
Coding: c.4929G>A
MANE Select: NM_013275
dbSNP: rs142939070
Type: single nucleotide variant
Location: chr16:89281613 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.44
Residue 1643: 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.Pro1643Gln Uncertain significance ★★ ⚠ same residue
ANKRD11 p.Pro1643Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro1643 (accessed [today's date]).

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