Is AASS p.His181Pro (c.542A>C) pathogenic?

AASS p.His181Pro (c.542A>C) is classified Uncertain significance in AASS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely pathogenic (0.8758); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AASS p.His181Pro (c.542A>C)?

AASS p.His181Pro (c.542A>C) is associated with Inborn genetic diseases (ClinVar).

How common is AASS p.His181Pro (c.542A>C) in the general population?

AASS p.His181Pro (c.542A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AASS p.His181Pro (c.542A>C)?

AlphaMissense predicts likely pathogenic (score 0.8758) — an in-silico prediction, not a clinical call.

AASS p.His181Pro

c.542A>C · VCV3265171

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8758 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8758	likely pathogenic
REVEL	0.691	pathogenic-leaning
SaProt	LLR -15.33	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 7.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 57 kb · p 0.0048 · regional, not allelic
Overall
CADD	31.0	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: AASS
Protein: p.His181Pro
Coding: c.542A>C
MANE Select: NM_005763
Type: single nucleotide variant
Location: chr7:122118452 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.73 · 9 PDB
Residue 181: the 'lysine-ketoglutarate reductase' region; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AASS p.His181= Likely benign ★ same residue
AASS p.Asn34Lys Uncertain significance ★★ ⚠ same condition
AASS p.Asn865Ser Uncertain significance ★★ ⚠ same condition
AASS p.Gly167Cys Uncertain significance ★★ ⚠ same condition
AASS p.His846Arg Uncertain significance ★★ ⚠ same condition
AASS p.Ile491Met Uncertain significance ★★ ⚠ same condition
AASS p.Leu465Val Uncertain significance ★★ ⚠ same condition
AASS p.Ser474Leu Uncertain significance ★★ ⚠ 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/aass-p-his181pro (accessed [today's date]).

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