Is ASCC2 p.Ser93Phe (c.278C>T) pathogenic?

ASCC2 p.Ser93Phe (c.278C>T) is classified Uncertain significance in ASCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-24). AlphaMissense: likely pathogenic (0.7991); Ultra-rare (popmax 0.0347%, afr).

How common is ASCC2 p.Ser93Phe (c.278C>T) in the general population?

ASCC2 p.Ser93Phe (c.278C>T) is ultra-rare (popmax 0.0347%, afr) (gnomAD).

What do computational predictors say about ASCC2 p.Ser93Phe (c.278C>T)?

AlphaMissense predicts likely pathogenic (score 0.7991) — an in-silico prediction, not a clinical call.

ASCC2 p.Ser93Phe

c.278C>T · VCV3789033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7991 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0347%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7991	likely pathogenic
REVEL	0.779	moderately pathogenic-leaning
SaProt	LLR -13.02	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 43 kb · p 0.00015 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0347% African / African-American · 25/72,060 alleles

Filtering AF 0.024% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.00207% 32/1,543,964 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0347%	2,882
Remaining individualsnot grpmax-eligible	0.00506%	19,761
Admixed American	0.00207%	48,336
European (non-Finnish)	0.000262%	381,997

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.Ser93Phe
Coding: c.278C>T
MANE Select: NM_032204
Type: single nucleotide variant
Location: chr22:29825220 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15 · 2 PDB
Residue 93: 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
ASCC2 p.Ala26Val Uncertain significance ★ ⚠ same type
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-ser93phe (accessed [today's date]).

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