Is ASCC3 p.Phe485Ser (c.1454T>C) pathogenic?

ASCC3 p.Phe485Ser (c.1454T>C) is classified Uncertain significance in ASCC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-13). AlphaMissense: likely pathogenic (0.7975); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with ASCC3 p.Phe485Ser (c.1454T>C)?

ASCC3 p.Phe485Ser (c.1454T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ASCC3 p.Phe485Ser (c.1454T>C) in the general population?

ASCC3 p.Phe485Ser (c.1454T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ASCC3 p.Phe485Ser (c.1454T>C)?

AlphaMissense predicts likely pathogenic (score 0.7975) — an in-silico prediction, not a clinical call.

ASCC3 p.Phe485Ser

c.1454T>C · VCV3789117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7975 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7975	likely pathogenic
REVEL	0.726	pathogenic-leaning
SaProt	LLR -13.13	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 11	GERP 2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 291 kb · p 5e-15 · regional, not allelic
Overall
CADD	28.6	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 0.00167% Admixed American · 1/60,018 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,070 alleles · very rare exomes 5/1,461,832 · genomes 0/152,238 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,018
European (non-Finnish)	0.000339%	295,002

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: ASCC3
Protein: p.Phe485Ser
Coding: c.1454T>C
MANE Select: NM_006828
Type: single nucleotide variant
Location: chr6:100767287 (GRCh38)
Gene constraint: LOEUF 0.677 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.93 · 2 PDB
Residue 485: an α-helix

Full ASCC3 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

ASCC3 p.Ala1186Val Uncertain significance ★★ ⚠ same condition
ASCC3 p.Ala94Val Uncertain significance ★★ ⚠ same condition
ASCC3 p.Arg1808His Uncertain significance ★★ ⚠ same condition
ASCC3 p.Arg1835Cys Uncertain significance ★★ ⚠ same condition
ASCC3 p.Arg630Cys Uncertain significance ★★ ⚠ same condition
ASCC3 p.Asn1607Ser Uncertain significance ★★ ⚠ same condition
ASCC3 p.Asp292Asn Uncertain significance ★★ ⚠ same condition
ASCC3 p.Glu344Gly 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/ascc3-p-phe485ser (accessed [today's date]).

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