Is ANKRD13A p.Gln377Glu (c.1129C>G) pathogenic?

ANKRD13A p.Gln377Glu (c.1129C>G) is classified Uncertain significance in ANKRD13A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). AlphaMissense: likely benign (0.2043); Very rare (popmax 0.00144%, nfe).

How common is ANKRD13A p.Gln377Glu (c.1129C>G) in the general population?

ANKRD13A p.Gln377Glu (c.1129C>G) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about ANKRD13A p.Gln377Glu (c.1129C>G)?

AlphaMissense predicts likely benign (score 0.2043) — an in-silico prediction, not a clinical call.

ANKRD13A p.Gln377Glu

c.1129C>G · VCV3866801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2043 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2043	likely benign
REVEL	0.351	indeterminate
SaProt	LLR -11.32	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.28	acceptor loss, 3 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 38 kb · p 6.7e-06 · 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 0.00144% European (non-Finnish) · 17/1,179,834 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00116% 17/1,461,656 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: ANKRD13A
Protein: p.Gln377Glu
Coding: c.1129C>G
MANE Select: NM_033121
Type: single nucleotide variant
Location: chr12:110029530 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.08

Full ANKRD13A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD13A p.Ala522Thr Uncertain significance ★ ⚠ same type
ANKRD13A p.Ala527Ser Uncertain significance ★ ⚠ same type
ANKRD13A p.Ala65Val Uncertain significance ★ same type
ANKRD13A p.Arg156Cys Uncertain significance ★ ⚠ same type
ANKRD13A p.Arg156His Uncertain significance ★ ⚠ same type
ANKRD13A p.Arg174His Uncertain significance ★ ⚠ same type
ANKRD13A p.Arg201Leu Uncertain significance ★ ⚠ same type
ANKRD13A p.Arg210Cys 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/ankrd13a-p-gln377glu (accessed [today's date]).

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