Is ANKRD31 p.Glu845Asp (c.2535A>T) pathogenic?

ANKRD31 p.Glu845Asp (c.2535A>T) is classified Likely benign in ANKRD31 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1229); Rare (popmax 0.563%, sas).

How common is ANKRD31 p.Glu845Asp (c.2535A>T) in the general population?

ANKRD31 p.Glu845Asp (c.2535A>T) is rare (popmax 0.563%, sas) (gnomAD).

What do computational predictors say about ANKRD31 p.Glu845Asp (c.2535A>T)?

AlphaMissense predicts likely benign (score 0.1229) — an in-silico prediction, not a clinical call.

ANKRD31 p.Glu845Asp

c.2535A>T · rs573539643 · VCV732785

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1229 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.563%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1229	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -1.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 168 kb · p 0.00044 · regional, not allelic
Overall
CADD	15.79	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 0.563% South Asian · 473/84,042 alleles

Filtering AF 0.521% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.504%

Overall 0.0335% 514/1,536,374 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.563%	178
Remaining individualsnot grpmax-eligible	0.05%	1,999
Middle Eastern	0.0334%	2,990
Admixed American	0.00196%	50,928
African / African-American	0.00137%	73,088
European (non-Finnish)	0.000611%	163,760

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.Glu845Asp
Coding: c.2535A>T
MANE Select: NM_001372053
dbSNP: rs573539643
Type: single nucleotide variant
Location: chr5:75146876 (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-glu845asp (accessed [today's date]).

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