Is ANKRD11 p.Ala2326Val (c.6977C>T) pathogenic?

ANKRD11 p.Ala2326Val (c.6977C>T) is classified Benign/Likely benign in ANKRD11 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-12). AlphaMissense: likely benign (0.0806); Rare (popmax 0.219%, afr); Associated with Inborn genetic diseases.

What condition is associated with ANKRD11 p.Ala2326Val (c.6977C>T)?

ANKRD11 p.Ala2326Val (c.6977C>T) is associated with Inborn genetic diseases, KBG syndrome (ClinVar).

How common is ANKRD11 p.Ala2326Val (c.6977C>T) in the general population?

ANKRD11 p.Ala2326Val (c.6977C>T) is rare (popmax 0.219%, afr) (gnomAD).

What do computational predictors say about ANKRD11 p.Ala2326Val (c.6977C>T)?

AlphaMissense predicts likely benign (score 0.0806) — an in-silico prediction, not a clinical call.

ANKRD11 p.Ala2326Val

c.6977C>T · rs576742682 · VCV1228814

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0806 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.219%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0806	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -7.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.27, phastCons 0.29
Regional constraint	o/e 0.76	unconstrained · MANE · 357 bp · p 0.0011 · regional, not allelic
Overall
CADD	11.62	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.219% African / African-American · 154/70,458 alleles

Filtering AF 0.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.18%

Overall 0.013% 187/1,434,820 alleles · rare exomes 79/1,283,158 · genomes 108/151,662 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.219%	458
Admixed American	0.0355%	2,814
Remaining individualsnot grpmax-eligible	0.0215%	4,653
South Asian	0.00262%	38,234
East Asian	0.00247%	40,550
European (non-Finnish)	0.000186%	537,204

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.Ala2326Val
Coding: c.6977C>T
MANE Select: NM_013275
dbSNP: rs576742682
Type: single nucleotide variant
Location: chr16:89279565 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 39.44
Residue 2326: the 'disordered' region

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.Ala2326Asp Uncertain significance ★★ ⚠ same residue
ANKRD11 p.Ala2326Gly Benign/Likely benign ★★ same residue
ANKRD11 p.Ala2326= Likely benign ★ same residue
ANKRD11 p.Ala2326fs Pathogenic ★ 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

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-ala2326val (accessed [today's date]).

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