Is HAP1 p.Asp339Asn (c.1015G>A) pathogenic?

HAP1 p.Asp339Asn (c.1015G>A) is classified Likely benign in HAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-03-15). AlphaMissense: likely benign (0.1038); Rare (popmax 0.254%, eas); Associated with HAP1-related disorder.

What condition is associated with HAP1 p.Asp339Asn (c.1015G>A)?

HAP1 p.Asp339Asn (c.1015G>A) is associated with HAP1-related disorder (ClinVar).

How common is HAP1 p.Asp339Asn (c.1015G>A) in the general population?

HAP1 p.Asp339Asn (c.1015G>A) is rare (popmax 0.254%, eas) (gnomAD).

What do computational predictors say about HAP1 p.Asp339Asn (c.1015G>A)?

AlphaMissense predicts likely benign (score 0.1038) — an in-silico prediction, not a clinical call.

HAP1 p.Asp339Asn

c.1015G>A · rs782208161 · VCV3054149

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1038 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.254%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

HAP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1038	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -5.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.5	GERP -2.4
Regional constraint	o/e 1.05	unconstrained · MANE · 9,930 bp · p 0.16 · regional, not allelic
Overall
CADD	14.68	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 0.254% East Asian · 114/44,860 alleles

Filtering AF 0.216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.202%

Overall 0.00881% 142/1,612,634 alleles · rare exomes 136/1,460,352 · genomes 6/152,282 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.254%	394
South Asian	0.00329%	30,351
European (non-Finnish)	0.00212%	47,145

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: HAP1
Protein: p.Asp339Asn
Coding: c.1015G>A
MANE Select: NM_177977
dbSNP: rs782208161
Type: single nucleotide variant
Location: chr17:41731547 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.28
Residue 339: the hap1 n-terminal domain

Full HAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

HAP1-related disorder

Similar variants

HAP1 c.1201-4C>T Likely benign same condition
HAP1 c.1201-7C>T Likely benign same condition
HAP1 c.470-7C>G Likely benign same condition
HAP1 p.Ala21= Likely benign same condition
HAP1 p.Ala505Val Benign same condition
HAP1 p.Arg116Trp Likely benign same condition
HAP1 p.Leu408Phe Benign ⚠ same condition
HAP1 p.Pro187His Likely benign 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/hap1-p-asp339asn (accessed [today's date]).

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