Is ANKRD11 p.Asp352= (c.1056C>T) pathogenic?

ANKRD11 p.Asp352= (c.1056C>T) is classified Benign/Likely benign in ANKRD11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-16). Ultra-rare (popmax 0.0164%, mid); Associated with KBG syndrome.

What condition is associated with ANKRD11 p.Asp352= (c.1056C>T)?

ANKRD11 p.Asp352= (c.1056C>T) is associated with KBG syndrome (ClinVar).

How common is ANKRD11 p.Asp352= (c.1056C>T) in the general population?

ANKRD11 p.Asp352= (c.1056C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

ANKRD11 p.Asp352=

c.1056C>T · rs149211555 · VCV2905407

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

KBG syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.6	GERP -3.5
Overall
CADD	1.098	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00198% 32/1,614,022 alleles · ultra-rare exomes 25/1,461,890 · genomes 7/152,132 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Finnishnot grpmax-eligible	0.00937%	10,670
African / African-American	0.00401%	24,965
South Asian	0.00329%	30,363
East Asian	0.00223%	44,890
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.00144%	69,414

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.Asp352=
Coding: c.1056C>T
MANE Select: NM_013275
dbSNP: rs149211555
Type: single nucleotide variant
Location: chr16:89285486 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.44
Residue 352: 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.Asp352Glu 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-asp352 (accessed [today's date]).

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