Is ASCC1 p.Leu320Phe (c.960G>T) pathogenic?

ASCC1 p.Leu320Phe (c.960G>T) is classified Uncertain significance in ASCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-30). Very rare (popmax 0.00156%, nfe).

How common is ASCC1 p.Leu320Phe (c.960G>T) in the general population?

ASCC1 p.Leu320Phe (c.960G>T) is very rare (popmax 0.00156%, nfe) (gnomAD).

ASCC1 p.Leu320Phe

c.960G>T · rs996055212 · VCV2139736

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00156%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.101	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -5.4
Regional constraint	o/e 0.88	unconstrained · MANE · 116 kb · p 0.011 · regional, not allelic
Overall
CADD	3.158	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00156% European (non-Finnish) · 18/1,150,458 alleles

Filtering AF 0.000978% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000807%

Overall 0.00126% 20/1,581,228 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00326%	30,706
European (non-Finnish)grpmax	0.00156%	63,915

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu320Phe
Coding: c.960G>T
MANE Select: NM_001198800
dbSNP: rs996055212
Type: single nucleotide variant
Location: chr10:72097448 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.70 · 1 PDB

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

Similar variants

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
ASCC1 p.Gln262Ter 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-leu320phe (accessed [today's date]).

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