Is ANKRD35 p.Arg510Pro (c.1529G>C) pathogenic?

ANKRD35 p.Arg510Pro (c.1529G>C) is classified Uncertain significance in ANKRD35 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: ambiguous (0.4666); Ultra-rare (popmax 0.0111%, eas).

How common is ANKRD35 p.Arg510Pro (c.1529G>C) in the general population?

ANKRD35 p.Arg510Pro (c.1529G>C) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about ANKRD35 p.Arg510Pro (c.1529G>C)?

AlphaMissense predicts ambiguous (score 0.4666) — an in-silico prediction, not a clinical call.

ANKRD35 p.Arg510Pro

c.1529G>C · rs201815402 · VCV2589025

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4666 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Computational evidence

Protein change
AlphaMissense	0.4666	ambiguous
SaProt	LLR -11.82	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -0.37, phastCons 0.15
Regional constraint	o/e 1.01	unconstrained · MANE · 18 kb · p 0.78 · regional, not allelic
Overall
CADD	20.2	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 0.0111% East Asian · 5/44,880 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.00626% 101/1,614,178 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,976
South Asian	0.011%	9,108
European (non-Finnish)	0.00636%	15,734
Finnishnot grpmax-eligible	0.00625%	16,009
Admixed American	0.005%	20,007
African / African-American	0.004%	25,021
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Arg510Pro
Coding: c.1529G>C
MANE Select: NM_144698
dbSNP: rs201815402
Type: single nucleotide variant
Location: chr1:145873240 (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-arg510pro (accessed [today's date]).

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