Is ASTE1 p.Cys115Arg (c.343T>C) pathogenic?

ASTE1 p.Cys115Arg (c.343T>C) is classified Uncertain significance in ASTE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-03). AlphaMissense: likely pathogenic (0.7776); Very rare (popmax 0.00134%, afr).

How common is ASTE1 p.Cys115Arg (c.343T>C) in the general population?

ASTE1 p.Cys115Arg (c.343T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ASTE1 p.Cys115Arg (c.343T>C)?

AlphaMissense predicts likely pathogenic (score 0.7776) — an in-silico prediction, not a clinical call.

ASTE1 p.Cys115Arg

c.343T>C · VCV3790951

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7776 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7776	likely pathogenic
REVEL	0.235	benign-leaning
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.0008 · 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 0.00134% African / African-American · 1/74,764 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000373% 6/1,608,500 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,764
European (non-Finnish)	0.000425%	235,369

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: ASTE1
Protein: p.Cys115Arg
Coding: c.343T>C
MANE Select: NM_014065
Type: single nucleotide variant
Location: chr3:131024964 (GRCh38)
Gene constraint: LOEUF 1.291 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.40

Full ASTE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASTE1 p.Ala202Thr Uncertain significance ★ ⚠ same type
ASTE1 p.Ala219Val Uncertain significance ★ ⚠ same type
ASTE1 p.Ala239Thr Uncertain significance ★ ⚠ same type
ASTE1 p.Ala514Thr Uncertain significance ★ ⚠ same type
ASTE1 p.Ala69Pro Uncertain significance ★ ⚠ same type
ASTE1 p.Arg143Trp Uncertain significance ★ ⚠ same type
ASTE1 p.Arg240His Uncertain significance ★ ⚠ same type
ASTE1 p.Arg255Gln 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/aste1-p-cys115arg (accessed [today's date]).

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