Is ANKAR p.Cys1109Arg (c.3325T>C) pathogenic?

ANKAR p.Cys1109Arg (c.3325T>C) is classified Uncertain significance in ANKAR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely pathogenic (0.8362); Very rare (popmax 0.0017%, amr).

How common is ANKAR p.Cys1109Arg (c.3325T>C) in the general population?

ANKAR p.Cys1109Arg (c.3325T>C) is very rare (popmax 0.0017%, amr) (gnomAD).

What do computational predictors say about ANKAR p.Cys1109Arg (c.3325T>C)?

AlphaMissense predicts likely pathogenic (score 0.8362) — an in-silico prediction, not a clinical call.

ANKAR p.Cys1109Arg

c.3325T>C · rs2468535202 · VCV3120259

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8362 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8362	likely pathogenic
REVEL	0.755	pathogenic-leaning
SaProt	LLR -8.46	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.74 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 70 kb · p 0.0059 · regional, not allelic
Overall
CADD	25.6	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 0.0017% Admixed American · 1/58,904 alleles

Filtering AF 0.000765% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000606%

Overall 0.00117% 17/1,455,744 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0017%	58,904
Remaining individualsnot grpmax-eligible	0.0016%	62,316
European (non-Finnish)	0.00127%	78,531

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: ANKAR
Protein: p.Cys1109Arg
Coding: c.3325T>C
MANE Select: NM_001378068
dbSNP: rs2468535202
Type: single nucleotide variant
Location: chr2:189733131 (GRCh38)
Gene constraint: LOEUF 1.07 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.79

Full ANKAR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKAR p.Asn938= Benign ★★ same type
ANKAR p.Gln1419Leu Benign ★★ same type
ANKAR p.Ile1349= Benign ★★ same type
ANKAR p.Leu94Arg Benign ★★ same type
ANKAR p.Thr206Ala Benign ★★ same type
ANKAR p.Thr92= Benign ★★ same type
ANKAR p.Tyr1262Ser Benign ★★ same type
ANKAR p.Val776Ala Likely benign ★★ ⚠ same type

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/ankar-p-cys1109arg (accessed [today's date]).

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