Is EPYC p.Ala35Pro (c.103G>C) pathogenic?

EPYC p.Ala35Pro (c.103G>C) is classified Uncertain significance in EPYC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-20). AlphaMissense: likely benign (0.0974); Absent from gnomAD v4.1.

How common is EPYC p.Ala35Pro (c.103G>C) in the general population?

EPYC p.Ala35Pro (c.103G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPYC p.Ala35Pro (c.103G>C)?

AlphaMissense predicts likely benign (score 0.0974) — an in-silico prediction, not a clinical call.

EPYC p.Ala35Pro

c.103G>C · rs1391181833 · VCV3090010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0974 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0974	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -5.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.092	GERP -0.68, phastCons 0.002
Regional constraint	o/e 1.00	unconstrained · MANE · 38 kb · p 0.94 · regional, not allelic
Overall
CADD	15.51	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EPYC
Protein: p.Ala35Pro
Coding: c.103G>C
MANE Select: NM_004950
dbSNP: rs1391181833
Type: single nucleotide variant
Location: chr12:91002463 (GRCh38)
Gene constraint: LOEUF 1.396 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.83

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

Similar variants

EPYC p.Ala137Val Uncertain significance ★ ⚠ same type
EPYC p.Ala16Asp Uncertain significance ★ ⚠ same type
EPYC p.Ala16Thr Uncertain significance ★ ⚠ same type
EPYC p.Arg194Gln Uncertain significance ★ ⚠ same type
EPYC p.Arg199Cys Uncertain significance ★ ⚠ same type
EPYC p.Arg199His Uncertain significance ★ ⚠ same type
EPYC p.Arg261Gln Uncertain significance ★ ⚠ same type
EPYC p.Arg288His 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/epyc-p-ala35pro (accessed [today's date]).

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