Is HOXA13 p.Leu26Val (c.76C>G) pathogenic?

HOXA13 p.Leu26Val (c.76C>G) is classified Uncertain significance in HOXA13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.1098); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with HOXA13 p.Leu26Val (c.76C>G)?

HOXA13 p.Leu26Val (c.76C>G) is associated with Inborn genetic diseases (ClinVar).

How common is HOXA13 p.Leu26Val (c.76C>G) in the general population?

HOXA13 p.Leu26Val (c.76C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HOXA13 p.Leu26Val (c.76C>G)?

AlphaMissense predicts likely benign (score 0.1098) — an in-silico prediction, not a clinical call.

HOXA13 p.Leu26Val

c.76C>G · VCV4035888

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1098 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1098	likely benign
REVEL	0.294	indeterminate
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP -0.53, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,876 bp · p 0.31 · regional, not allelic
Overall
CADD	16.76	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HOXA13
Protein: p.Leu26Val
Coding: c.76C>G
MANE Select: NM_000522
Type: single nucleotide variant
Location: chr7:27200002 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 56.23 · 1 PDB

Full HOXA13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HOXA13 p.Ala132Thr Uncertain significance ★★ ⚠ same condition
HOXA13 p.Ala92Gly Uncertain significance ★★ ⚠ same condition
HOXA13 p.Arg88His Uncertain significance ★★ ⚠ same condition
HOXA13 p.Asn189Ser Uncertain significance ★★ ⚠ same condition
HOXA13 p.Asn283Ser Uncertain significance ★★ ⚠ same condition
HOXA13 p.Gly110Trp Uncertain significance ★★ ⚠ same condition
HOXA13 p.Gly177Ser Uncertain significance ★★ ⚠ same condition
HOXA13 p.Met184Lys Uncertain significance ★★ ⚠ same condition

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/hoxa13-p-leu26val (accessed [today's date]).

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