Is ANKRD13B p.Ser331Asn (c.992G>A) pathogenic?

ANKRD13B p.Ser331Asn (c.992G>A) is classified Uncertain significance in ANKRD13B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.2018); Very rare (popmax 8.48e-05%, nfe).

How common is ANKRD13B p.Ser331Asn (c.992G>A) in the general population?

ANKRD13B p.Ser331Asn (c.992G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ANKRD13B p.Ser331Asn (c.992G>A)?

AlphaMissense predicts likely benign (score 0.2018) — an in-silico prediction, not a clinical call.

ANKRD13B p.Ser331Asn

c.992G>A · VCV3544105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2018 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2018	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 4,669 bp · p 6.2e-17 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,436 alleles

Overall 6.85e-05% 1/1,460,736 alleles · very rare

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: ANKRD13B
Protein: p.Ser331Asn
Coding: c.992G>A
MANE Select: NM_152345
Type: single nucleotide variant
Location: chr17:29611898 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.46

Full ANKRD13B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD13B p.Arg26Cys Uncertain significance ★★ ⚠ same type
ANKRD13B p.Ala114Val Uncertain significance ★ ⚠ same type
ANKRD13B p.Ala223Thr Uncertain significance ★ ⚠ same type
ANKRD13B p.Ala236Val Uncertain significance ★ ⚠ same type
ANKRD13B p.Ala553Thr Uncertain significance ★ ⚠ same type
ANKRD13B p.Ala562Gly Uncertain significance ★ ⚠ same type
ANKRD13B p.Ala69Val Uncertain significance ★ ⚠ same type
ANKRD13B p.Arg102Gln 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/ankrd13b-p-ser331asn (accessed [today's date]).

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