Is ASNS p.Pro211His (c.632C>A) pathogenic?

ASNS p.Pro211His (c.632C>A) is classified Uncertain significance in ASNS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-22). AlphaMissense: likely pathogenic (0.8905); Absent from gnomAD v4.1.

How common is ASNS p.Pro211His (c.632C>A) in the general population?

ASNS p.Pro211His (c.632C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASNS p.Pro211His (c.632C>A)?

AlphaMissense predicts likely pathogenic (score 0.8905) — an in-silico prediction, not a clinical call.

ASNS p.Pro211His

c.632C>A · rs2115659026 · VCV1303959

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8905 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8905	likely pathogenic
REVEL	0.33	indeterminate
SaProt	LLR -10.40	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 9.8	GERP 0.92, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 17 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	24.6	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: ASNS
Protein: p.Pro211His
Coding: c.632C>A
MANE Select: NM_001673
dbSNP: rs2115659026
Type: single nucleotide variant
Location: chr7:97859254 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB

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

Similar variants

ASNS p.Pro211Ser Uncertain significance ★★ ⚠ same residue
ASNS p.Pro211= Likely benign ★ same residue
ASNS c.1030+1G>A Likely pathogenic ★★ same type
ASNS c.1138-1G>A Likely pathogenic ★★ same type
ASNS c.1239-2A>T Likely pathogenic ★★ same type
ASNS c.1320+1G>C Likely pathogenic ★★ same type
ASNS c.1320+1G>T Likely pathogenic ★★ same type
ASNS c.1321-1G>A Likely pathogenic ★★ 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/asns-p-pro211his (accessed [today's date]).

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