Is ANKRD35 p.Arg306Trp (c.916C>T) pathogenic?

ANKRD35 p.Arg306Trp (c.916C>T) is classified Uncertain significance in ANKRD35 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-21). AlphaMissense: likely benign (0.1146); Ultra-rare (popmax 0.0106%, nfe).

How common is ANKRD35 p.Arg306Trp (c.916C>T) in the general population?

ANKRD35 p.Arg306Trp (c.916C>T) is ultra-rare (popmax 0.0106%, nfe) (gnomAD).

What do computational predictors say about ANKRD35 p.Arg306Trp (c.916C>T)?

AlphaMissense predicts likely benign (score 0.1146) — an in-silico prediction, not a clinical call.

ANKRD35 p.Arg306Trp

c.916C>T · VCV3297528

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1146 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1146	likely benign
SaProt	LLR -10.80	damaging
⇒ SaProt calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 18 kb · p 0.78 · regional, not allelic
Overall
CADD	19.9	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 0.0106% European (non-Finnish) · 125/1,179,434 alleles

Filtering AF 0.00906% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00845%

Overall 0.00887% 143/1,612,756 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0106%	9,435
Remaining individualsnot grpmax-eligible	0.00961%	10,408
East Asian	0.00668%	14,959
Finnishnot grpmax-eligible	0.00469%	21,310
South Asian	0.0033%	30,300
African / African-American	0.00267%	37,430
Admixed American	0.00167%	59,746

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.Arg306Trp
Coding: c.916C>T
MANE Select: NM_144698
Type: single nucleotide variant
Location: chr1:145873853 (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-arg306trp (accessed [today's date]).

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