Is ALAS2 p.Ter588Arg (c.1762T>C) pathogenic?

ALAS2 p.Ter588Arg (c.1762T>C) is classified Likely pathogenic in ALAS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-24). Absent from gnomAD v4.1; Associated with X-linked sideroblastic anemia 1.

What condition is associated with ALAS2 p.Ter588Arg (c.1762T>C)?

ALAS2 p.Ter588Arg (c.1762T>C) is associated with X-linked sideroblastic anemia 1 (ClinVar).

How common is ALAS2 p.Ter588Arg (c.1762T>C) in the general population?

ALAS2 p.Ter588Arg (c.1762T>C) is absent from gnomAD v4.1 (gnomAD).

How is X-linked sideroblastic anemia inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ALAS2 p.Ter588Arg

c.1762T>C · VCV3731274

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,207,718)

Conditions

X-linked sideroblastic anemia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.9, phastCons 1
Overall
CADD	16.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,207,718). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALAS2
Protein: p.Ter588Arg
Coding: c.1762T>C
MANE Select: NM_000032
Type: single nucleotide variant
Location: chrX:55009182 (GRCh38)
Structure: AlphaFold pLDDT 82.76 · 27 PDB

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

Disease context

X-linked sideroblastic anemia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked sideroblastic anemia (Orphanet):

Inheritance: X-linked recessive
Onset: All ages

Similar variants

ALAS2 p.Arg411Cys Pathogenic ★★ same condition
ALAS2 p.Arg452Cys Pathogenic ★★ same condition
ALAS2 p.Ala336Asp Uncertain significance ★★ ⚠ same condition
ALAS2 p.Cys471Arg Uncertain significance ★★ ⚠ same condition
ALAS2 c.824-15C>T Benign ★★ same condition
ALAS2 c.*124C>T Benign/Likely benign ★★ same condition
ALAS2 c.*56A>C Benign ★★ same condition
ALAS2 p.Ala542= Benign ★★ 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/alas2-p-ter588arg (accessed [today's date]).

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