Is ASCC2 p.Arg365Trp (c.1093C>T) pathogenic?

ASCC2 p.Arg365Trp (c.1093C>T) is classified Uncertain significance in ASCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.1922); Very rare (popmax 0.00549%, sas).

How common is ASCC2 p.Arg365Trp (c.1093C>T) in the general population?

ASCC2 p.Arg365Trp (c.1093C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about ASCC2 p.Arg365Trp (c.1093C>T)?

AlphaMissense predicts likely benign (score 0.1922) — an in-silico prediction, not a clinical call.

ASCC2 p.Arg365Trp

c.1093C>T · VCV4153121

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1922 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1922	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -11.25	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 43 kb · p 0.00015 · regional, not allelic
Overall
CADD	24.1	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 0.00549% South Asian · 5/91,082 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00254% 41/1,613,972 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,216
European (non-Finnish)	0.00288%	34,707
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00134%	74,880

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: ASCC2
Protein: p.Arg365Trp
Coding: c.1093C>T
MANE Select: NM_032204
Type: single nucleotide variant
Location: chr22:29806283 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15 · 2 PDB
Residue 365: an α-helix

Full ASCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASCC2 p.Ala258Val Uncertain significance ★ ⚠ same type
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ASCC2 p.Ala414Ser Uncertain significance ★ ⚠ same type
ASCC2 p.Ala457Val Uncertain significance ★ ⚠ same type
ASCC2 p.Ala50Thr Uncertain significance ★ ⚠ same type
ASCC2 p.Ala732Asp Uncertain significance ★ ⚠ same type
ASCC2 p.Ala735Val Uncertain significance ★ ⚠ same type
ASCC2 p.Ala738Gly 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/ascc2-p-arg365trp (accessed [today's date]).

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