Is ASCC1 p.Val3Ala (c.8T>C) pathogenic?

ASCC1 p.Val3Ala (c.8T>C) is classified Likely benign in ASCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-25). AlphaMissense: likely pathogenic (0.7481); Rare (popmax 0.175%, afr).

How common is ASCC1 p.Val3Ala (c.8T>C) in the general population?

ASCC1 p.Val3Ala (c.8T>C) is rare (popmax 0.175%, afr) (gnomAD).

What do computational predictors say about ASCC1 p.Val3Ala (c.8T>C)?

AlphaMissense predicts likely pathogenic (score 0.7481) — an in-silico prediction, not a clinical call.

ASCC1 p.Val3Ala

c.8T>C · rs114537787 · VCV1565162

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7481 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.175%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7481	likely pathogenic
REVEL	0.168	moderately benign-leaning
SaProt	LLR -5.94	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 0.61, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 116 kb · p 0.011 · regional, not allelic
Overall
CADD	25.3	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 0.175% African / African-American · 131/74,954 alleles

Filtering AF 0.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.141%

Overall 0.00932% 150/1,610,196 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.175%	572
Admixed American	0.015%	6,667
Remaining individualsnot grpmax-eligible	0.0144%	6,928
European (non-Finnish)	8.5e-05%	1,176,615

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: ASCC1
Protein: p.Val3Ala
Coding: c.8T>C
MANE Select: NM_001198800
dbSNP: rs114537787
Type: single nucleotide variant
Location: chr10:72213291 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.70 · 1 PDB
Residue 3: the 'required for interaction with ascc3' region

Full ASCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASCC1 p.Val3Leu Uncertain significance ★ ⚠ same residue
ASCC1 c.311-2A>G Pathogenic ★★ same type
ASCC1 c.626+1G>A Pathogenic/Likely pathogenic ★★ same type
ASCC1 c.871+1G>A Pathogenic/Likely pathogenic ★★ same type
ASCC1 p.Arg110Ter Pathogenic ★★ same type
ASCC1 p.Arg117Ter Pathogenic ★★ same type
ASCC1 p.Arg128Ter Pathogenic ★★ same type
ASCC1 p.Gln195Ter Pathogenic/Likely pathogenic ★★ 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/ascc1-p-val3ala (accessed [today's date]).

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