Is ANKRD31 p.Arg484Trp (c.1450C>T) pathogenic?

ANKRD31 p.Arg484Trp (c.1450C>T) is classified Uncertain significance in ANKRD31 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: likely benign (0.2084); Rare (popmax 0.399%, afr).

How common is ANKRD31 p.Arg484Trp (c.1450C>T) in the general population?

ANKRD31 p.Arg484Trp (c.1450C>T) is rare (popmax 0.399%, afr) (gnomAD).

What do computational predictors say about ANKRD31 p.Arg484Trp (c.1450C>T)?

AlphaMissense predicts likely benign (score 0.2084) — an in-silico prediction, not a clinical call.

ANKRD31 p.Arg484Trp

c.1450C>T · rs184949434 · VCV2229660

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2084 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.399%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2084	likely benign
REVEL	0.357	indeterminate
SaProt	LLR -11.28	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 0.38, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 168 kb · p 0.00044 · regional, not allelic
Overall
CADD	26.1	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 0.399% African / African-American · 291/72,964 alleles

Filtering AF 0.361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.346%

Overall 0.0233% 358/1,535,200 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.399%	251
Middle Eastern	0.0507%	1,971
Remaining individualsnot grpmax-eligible	0.0367%	2,725
Admixed American	0.0295%	3,391
South Asian	0.0107%	9,308
European (non-Finnish)	0.00157%	63,662

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: ANKRD31
Protein: p.Arg484Trp
Coding: c.1450C>T
MANE Select: NM_001372053
dbSNP: rs184949434
Type: single nucleotide variant
Location: chr5:75188607 (GRCh38)
Gene constraint: LOEUF 0.844 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.08

Full ANKRD31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD31 p.Arg1353Gln Benign ★★ same type
ANKRD31 p.Asn192Ile Benign ★★ same type
ANKRD31 c.1565-2A>G Pathogenic ★ same type
ANKRD31 p.Gln329Ter Pathogenic ★ same type
ANKRD31 p.Ala1011Asp Uncertain significance ★ ⚠ same type
ANKRD31 p.Ala1021Thr Uncertain significance ★ ⚠ same type
ANKRD31 p.Ala1294Thr Uncertain significance ★ ⚠ same type
ANKRD31 p.Ala1302Thr 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/ankrd31-p-arg484trp (accessed [today's date]).

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