Is HAP1 p.Pro187His (c.560C>A) pathogenic?

HAP1 p.Pro187His (c.560C>A) is classified Likely benign in HAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-04). AlphaMissense: likely benign (0.1492); Rare (popmax 0.244%, nfe); Associated with HAP1-related disorder.

What condition is associated with HAP1 p.Pro187His (c.560C>A)?

HAP1 p.Pro187His (c.560C>A) is associated with HAP1-related disorder (ClinVar).

How common is HAP1 p.Pro187His (c.560C>A) in the general population?

HAP1 p.Pro187His (c.560C>A) is rare (popmax 0.244%, nfe) (gnomAD).

What do computational predictors say about HAP1 p.Pro187His (c.560C>A)?

AlphaMissense predicts likely benign (score 0.1492) — an in-silico prediction, not a clinical call.

HAP1 p.Pro187His

c.560C>A · rs142535684 · VCV3038606

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1492 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.244%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

HAP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1492	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -8.01	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 0.1	GERP -0.064
Regional constraint	o/e 1.05	unconstrained · MANE · 9,930 bp · p 0.16 · regional, not allelic
Overall
CADD	14.08	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 0.244% European (non-Finnish) · 2,875/1,179,928 alleles

Filtering AF 0.236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.233%

Overall 0.195% 3,150/1,613,968 alleles · rare exomes 2,974/1,461,680 · genomes 176/152,288 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.244%	410
Remaining individualsnot grpmax-eligible	0.142%	702
South Asian	0.0978%	1,023
Admixed American	0.0917%	1,091
African / African-American	0.0413%	2,420
Middle Eastern	0.0165%	6,062
Finnishnot grpmax-eligible	0.0141%	7,112
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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.Pro187His
Coding: c.560C>A
MANE Select: NM_177977
dbSNP: rs142535684
Type: single nucleotide variant
Location: chr17:41732384 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.28
Residue 187: 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.Asp339Asn Likely benign same condition
HAP1 p.Leu408Phe 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-pro187his (accessed [today's date]).

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