Is ANKRD11 p.Pro260= (c.780G>A) pathogenic?

ANKRD11 p.Pro260= (c.780G>A) is classified Likely benign in ANKRD11 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-09-17). Very rare (popmax 0.005%, amr); Associated with KBG syndrome.

What condition is associated with ANKRD11 p.Pro260= (c.780G>A)?

ANKRD11 p.Pro260= (c.780G>A) is associated with KBG syndrome (ClinVar).

How common is ANKRD11 p.Pro260= (c.780G>A) in the general population?

ANKRD11 p.Pro260= (c.780G>A) is very rare (popmax 0.005%, amr) (gnomAD).

ANKRD11 p.Pro260=

c.780G>A · rs377284083 · VCV1109830

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, 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 0.44	GERP -3.7, phastCons 0.84
Overall
CADD	11.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,012 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00248% 40/1,613,890 alleles · very rare exomes 37/1,461,672 · genomes 3/152,218 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,004
East Asian	0.00446%	22,445
Finnishnot grpmax-eligible	0.00313%	31,916
European (non-Finnish)	0.00263%	38,066
African / African-American	0.00133%	74,936
South Asian	0.0011%	91,094

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.Pro260=
Coding: c.780G>A
MANE Select: NM_013275
dbSNP: rs377284083
Type: single nucleotide variant
Location: chr16:89286151 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.44

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-pro260 (accessed [today's date]).

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