Is ASAP1 p.Arg212His (c.635G>A) pathogenic?

ASAP1 p.Arg212His (c.635G>A) is classified Uncertain significance in ASAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-28). AlphaMissense: likely pathogenic (0.8351); Very rare (popmax 0.00267%, afr).

How common is ASAP1 p.Arg212His (c.635G>A) in the general population?

ASAP1 p.Arg212His (c.635G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ASAP1 p.Arg212His (c.635G>A)?

AlphaMissense predicts likely pathogenic (score 0.8351) — an in-silico prediction, not a clinical call.

ASAP1 p.Arg212His

c.635G>A · rs200268356 · VCV2600593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8351 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8351	likely pathogenic
REVEL	0.501	indeterminate
SaProt	LLR -11.90	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 35 kb · p 6e-11 · regional, not allelic
Overall
CADD	27.4	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

Grpmax group 0.00267% African / African-American · 2/74,790 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000744% 12/1,612,624 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,395
East Asian	0.00223%	44,868
Admixed American	0.00167%	59,702
Remaining individualsnot grpmax-eligible	0.0016%	62,408
European (non-Finnish)	0.000593%	168,512

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: ASAP1
Protein: p.Arg212His
Coding: c.635G>A
MANE Select: NM_018482
dbSNP: rs200268356
Type: single nucleotide variant
Location: chr8:130180776 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.05 · 5 PDB

Full ASAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASAP1 p.Gln263= Benign ★★ same type
ASAP1 p.Ala1035Gly Uncertain significance ★ ⚠ same type
ASAP1 p.Ala429Val Uncertain significance ★ ⚠ same type
ASAP1 p.Ala914Gly Uncertain significance ★ ⚠ same type
ASAP1 p.Arg447Gln Uncertain significance ★ ⚠ same type
ASAP1 p.Arg710Ter Uncertain significance ★ same type
ASAP1 p.Arg764Gln Uncertain significance ★ ⚠ same type
ASAP1 p.Asn134Tyr 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/asap1-p-arg212his (accessed [today's date]).

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