Is ASAP3 p.His336Pro (c.1007A>C) pathogenic?

ASAP3 p.His336Pro (c.1007A>C) is classified Uncertain significance in ASAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-18). AlphaMissense: likely pathogenic (0.9401); Absent from gnomAD v4.1.

How common is ASAP3 p.His336Pro (c.1007A>C) in the general population?

ASAP3 p.His336Pro (c.1007A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASAP3 p.His336Pro (c.1007A>C)?

AlphaMissense predicts likely pathogenic (score 0.9401) — an in-silico prediction, not a clinical call.

ASAP3 p.His336Pro

c.1007A>C · VCV3950801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9401 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9401	likely pathogenic · top 7% in ASAP3
REVEL	0.798	moderately pathogenic-leaning
SaProt	LLR -10.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: ASAP3
Protein: p.His336Pro
Coding: c.1007A>C
MANE Select: NM_017707
Type: single nucleotide variant
Location: chr1:23439168 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.62 · 4 PDB
Residue 336: the ph domain

Full ASAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASAP3 p.Asp314= Benign ★★ same type
ASAP3 p.Glu377Ala Benign ★★ ⚠ same type
ASAP3 p.Leu147= Benign ★★ same type
ASAP3 p.Ala103Thr Uncertain significance ★ ⚠ same type
ASAP3 p.Ala221Thr Uncertain significance ★ ⚠ same type
ASAP3 p.Ala244Val Uncertain significance ★ ⚠ same type
ASAP3 p.Ala415Val Uncertain significance ★ ⚠ same type
ASAP3 p.Ala566Thr 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/asap3-p-his336pro (accessed [today's date]).

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