Is ASCC1 p.Ser91Phe (c.272C>T) pathogenic?

ASCC1 p.Ser91Phe (c.272C>T) is classified Uncertain significance in ASCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.2266); Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with ASCC1 p.Ser91Phe (c.272C>T)?

ASCC1 p.Ser91Phe (c.272C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ASCC1 p.Ser91Phe (c.272C>T) in the general population?

ASCC1 p.Ser91Phe (c.272C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about ASCC1 p.Ser91Phe (c.272C>T)?

AlphaMissense predicts likely benign (score 0.2266) — an in-silico prediction, not a clinical call.

ASCC1 p.Ser91Phe

c.272C>T · VCV4152920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2266 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2266	likely benign
REVEL	0.466	indeterminate
SaProt	LLR -6.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 116 kb · p 0.011 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S119F vs ClinVar S91F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,914 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,613,490 alleles · very rare

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.Ser91Phe
Coding: c.272C>T
MANE Select: NM_001198800
Type: single nucleotide variant
Location: chr10:72203465 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.70 · 1 PDB
Residue 91: the kh domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ASCC1 p.Ala300Val Uncertain significance ★★ ⚠ same condition
ASCC1 p.Arg14Gln Uncertain significance ★★ same condition
ASCC1 p.Arg77Ile Uncertain significance ★★ ⚠ same condition
ASCC1 p.Gln131His Uncertain significance ★★ ⚠ same condition
ASCC1 p.Gln24Arg Uncertain significance ★★ ⚠ same condition
ASCC1 p.Glu102Lys Uncertain significance ★★ ⚠ same condition
ASCC1 p.Gly302Ser Uncertain significance ★★ ⚠ same condition
ASCC1 p.Gly327Val Uncertain significance ★★ same condition

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-ser91phe (accessed [today's date]).

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