Is ALAS2 p.Asp190His (c.568G>C) pathogenic?

ALAS2 p.Asp190His (c.568G>C) is classified Uncertain significance in ALAS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.1913); Absent from gnomAD v4.1.

How common is ALAS2 p.Asp190His (c.568G>C) in the general population?

ALAS2 p.Asp190His (c.568G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALAS2 p.Asp190His (c.568G>C)?

AlphaMissense predicts likely benign (score 0.1913) — an in-silico prediction, not a clinical call.

ALAS2 p.Asp190His

c.568G>C · rs188389696 · VCV2690874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1913 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1913	likely benign
REVEL	0.65	pathogenic-leaning
SaProt	LLR -8.03	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.70 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.2	GERP -2.4, phastCons 0.99
Regional constraint	o/e 0.52	unconstrained · MANE · 8,973 bp · p 5.5e-15 · regional, not allelic
Overall
CADD	24.5	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

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: ALAS2
Protein: p.Asp190His
Coding: c.568G>C
MANE Select: NM_000032
dbSNP: rs188389696
Type: single nucleotide variant
Location: chrX:55021122 (GRCh38)
Structure: AlphaFold pLDDT 82.76 · 27 PDB
Residue 190: a β-strand

Full ALAS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALAS2 p.Asp190Val Pathogenic ⚠ same residue
ALAS2 p.Arg170Cys Pathogenic/Likely pathogenic ★★ same type
ALAS2 p.Arg411Cys Pathogenic ★★ same type
ALAS2 p.Arg452Cys Pathogenic ★★ same type
ALAS2 p.Arg452His Pathogenic ★★ ⚠ same type
ALAS2 p.Arg452Ser Pathogenic ★★ ⚠ same type
ALAS2 c.1168+4A>C Uncertain significance ★★ same type
ALAS2 p.Ala282Thr 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/alas2-p-asp190his (accessed [today's date]).

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