Is ANKRD11 p.Pro2083= (c.6249C>T) pathogenic?

ANKRD11 p.Pro2083= (c.6249C>T) is classified Likely benign in ANKRD11 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-02). Ultra-rare (popmax 0.0741%, sas); Associated with Inborn genetic diseases.

What condition is associated with ANKRD11 p.Pro2083= (c.6249C>T)?

ANKRD11 p.Pro2083= (c.6249C>T) is associated with Inborn genetic diseases, KBG syndrome (ClinVar).

How common is ANKRD11 p.Pro2083= (c.6249C>T) in the general population?

ANKRD11 p.Pro2083= (c.6249C>T) is ultra-rare (popmax 0.0741%, sas) (gnomAD).

ANKRD11 p.Pro2083=

c.6249C>T · rs753640103 · VCV1102061

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0741%, sas)

Conditions

Inborn genetic diseases

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 -1.4	GERP -3.1
Overall
CADD	1.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0741% South Asian · 67/90,406 alleles

Filtering AF 0.0598% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0546%

Overall 0.00863% 138/1,599,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0741%	1,349
Remaining individualsnot grpmax-eligible	0.00649%	15,420
European (non-Finnish)	0.00537%	18,627
Admixed American	0.00512%	19,515
African / African-American	0.00134%	74,534

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.Pro2083=
Coding: c.6249C>T
MANE Select: NM_013275
dbSNP: rs753640103
Type: single nucleotide variant
Location: chr16:89280293 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: KBG syndrome

Similar variants

ANKRD11 p.Pro2083Ser 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
ANKRD11 c.892+1G>A 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-pro2083 (accessed [today's date]).

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