Is ANKRD11 p.Pro1839= (c.5517C>T) pathogenic?

ANKRD11 p.Pro1839= (c.5517C>T) is classified Likely benign in ANKRD11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-20). Ultra-rare (popmax 0.0292%, eas); Associated with KBG syndrome.

What condition is associated with ANKRD11 p.Pro1839= (c.5517C>T)?

ANKRD11 p.Pro1839= (c.5517C>T) is associated with KBG syndrome (ClinVar).

How common is ANKRD11 p.Pro1839= (c.5517C>T) in the general population?

ANKRD11 p.Pro1839= (c.5517C>T) is ultra-rare (popmax 0.0292%, eas) (gnomAD).

ANKRD11 p.Pro1839=

c.5517C>T · rs775390865 · VCV2647067

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0292%, eas)

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 -2.3	GERP -2.2
Overall
CADD	0.417	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0292% East Asian · 13/44,584 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00138% 22/1,594,616 alleles · ultra-rare exomes 20/1,442,418 · genomes 2/152,198 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0292%	3,430
Middle Eastern	0.0167%	5,982
South Asian	0.00675%	14,821
Remaining individualsnot grpmax-eligible	0.00325%	30,771

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.Pro1839=
Coding: c.5517C>T
MANE Select: NM_013275
dbSNP: rs775390865
Type: single nucleotide variant
Location: chr16:89281025 (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 p.Pro1839Ser 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-pro1839 (accessed [today's date]).

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