Is ASNS p.His205Pro (c.614A>C) pathogenic?

ASNS p.His205Pro (c.614A>C) is classified Conflicting classifications of pathogenicity in ASNS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-03-04). AlphaMissense: likely pathogenic (0.6953); Very rare (popmax 0.000254%, nfe).

How common is ASNS p.His205Pro (c.614A>C) in the general population?

ASNS p.His205Pro (c.614A>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about ASNS p.His205Pro (c.614A>C)?

AlphaMissense predicts likely pathogenic (score 0.6953) — an in-silico prediction, not a clinical call.

ASNS p.His205Pro

c.614A>C · rs1252577998 · VCV1486990

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6953 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6953	likely pathogenic
REVEL	0.491	indeterminate
SaProt	LLR -11.31	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 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 17 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	24.7	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 0.000254% European (non-Finnish) · 3/1,180,024 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,050 alleles · very rare

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: ASNS
Protein: p.His205Pro
Coding: c.614A>C
MANE Select: NM_001673
dbSNP: rs1252577998
Type: single nucleotide variant
Location: chr7:97859272 (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 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
ASNS c.1476+1G>A Pathogenic ★★ same type
ASNS c.1476+2T>C 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-his205pro (accessed [today's date]).

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