Is ANKRD11 p.Pro2650= (c.7950C>T) pathogenic?

ANKRD11 p.Pro2650= (c.7950C>T) is classified Likely benign in ANKRD11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). Very rare (popmax 0.00123%, sas); Associated with KBG syndrome.

What condition is associated with ANKRD11 p.Pro2650= (c.7950C>T)?

ANKRD11 p.Pro2650= (c.7950C>T) is associated with KBG syndrome (ClinVar).

How common is ANKRD11 p.Pro2650= (c.7950C>T) in the general population?

ANKRD11 p.Pro2650= (c.7950C>T) is very rare (popmax 0.00123%, sas) (gnomAD).

ANKRD11 p.Pro2650=

c.7950C>T · VCV4534373

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00123%, sas)

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 4.9	GERP 1.6, phastCons 1
Overall
CADD	18.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00123% South Asian · 1/81,622 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 6e-05%

Overall 0.000466% 6/1,288,304 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00178%	56,184
South Asiangrpmax	0.00123%	81,622
European (non-Finnish)	0.000382%	261,635

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro2650=
Coding: c.7950C>T
MANE Select: NM_013275
Type: single nucleotide variant
Location: chr16:89268520 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.44
Residue 2650: 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 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-pro2650 (accessed [today's date]).

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