Is HAT1 p.Ile413Val (c.1237A>G) pathogenic?

HAT1 p.Ile413Val (c.1237A>G) is classified Uncertain significance in HAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). AlphaMissense: likely benign (0.0721); Absent from gnomAD v4.1.

How common is HAT1 p.Ile413Val (c.1237A>G) in the general population?

HAT1 p.Ile413Val (c.1237A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HAT1 p.Ile413Val (c.1237A>G)?

AlphaMissense predicts likely benign (score 0.0721) — an in-silico prediction, not a clinical call.

HAT1 p.Ile413Val

c.1237A>G · VCV3523992

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0721 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0721	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -6.42	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 7.9	GERP 0.29, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 61 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	17.41	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: HAT1
Protein: p.Ile413Val
Coding: c.1237A>G
MANE Select: NM_003642
Type: single nucleotide variant
Location: chr2:171983329 (GRCh38)
Gene constraint: LOEUF 1.439 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 93.01 · 3 PDB

Full HAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HAT1 p.Ala32Thr Uncertain significance ★ same type
HAT1 p.Arg330Ser Uncertain significance ★ ⚠ same type
HAT1 p.Arg349Gly Uncertain significance ★ ⚠ same type
HAT1 p.Arg349Lys Uncertain significance ★ ⚠ same type
HAT1 p.Arg410Trp Uncertain significance ★ ⚠ same type
HAT1 p.Arg411Cys Uncertain significance ★ ⚠ same type
HAT1 p.Asn122Lys Uncertain significance ★ ⚠ same type
HAT1 p.Asp47Gly 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/hat1-p-ile413val (accessed [today's date]).

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