Is ANKRD35 p.Arg981Gln (c.2942G>A) pathogenic?

ANKRD35 p.Arg981Gln (c.2942G>A) is classified Likely benign in ANKRD35 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-08). AlphaMissense: likely benign (0.0657); Ultra-rare (popmax 0.0117%, amr).

How common is ANKRD35 p.Arg981Gln (c.2942G>A) in the general population?

ANKRD35 p.Arg981Gln (c.2942G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about ANKRD35 p.Arg981Gln (c.2942G>A)?

AlphaMissense predicts likely benign (score 0.0657) — an in-silico prediction, not a clinical call.

ANKRD35 p.Arg981Gln

c.2942G>A · rs377017276 · VCV2228329

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0657 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0657	likely benign
SaProt	LLR -5.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.82	GERP -3.3, phastCons 0.011
Regional constraint	o/e 1.01	unconstrained · MANE · 18 kb · p 0.78 · regional, not allelic
Overall
CADD	1.474	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 0.0117% Admixed American · 7/60,022 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.00613% 99/1,614,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,575
African / African-American	0.00933%	10,723
European (non-Finnish)	0.00661%	15,127
South Asian	0.00549%	18,213
Remaining individualsnot grpmax-eligible	0.0032%	31,251

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: ANKRD35
Protein: p.Arg981Gln
Coding: c.2942G>A
MANE Select: NM_144698
dbSNP: rs377017276
Type: single nucleotide variant
Location: chr1:145867992 (GRCh38)
Gene constraint: LOEUF 1.071 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43

Full ANKRD35 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD35 p.Ala133Val Uncertain significance ★ ⚠ same type
ANKRD35 p.Ala144Thr Uncertain significance ★ ⚠ same type
ANKRD35 p.Ala202Gly Uncertain significance ★ ⚠ same type
ANKRD35 p.Ala212Thr Uncertain significance ★ ⚠ same type
ANKRD35 p.Ala241Ser Uncertain significance ★ ⚠ same type
ANKRD35 p.Ala480Ser Uncertain significance ★ ⚠ same type
ANKRD35 p.Ala486Glu Uncertain significance ★ ⚠ same type
ANKRD35 p.Ala521Thr Uncertain significance ★ ⚠ 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/ankrd35-p-arg981gln (accessed [today's date]).

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