Is EPOP p.Pro16Leu (c.47C>T) pathogenic?

EPOP p.Pro16Leu (c.47C>T) is classified Uncertain significance in EPOP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-23). AlphaMissense: likely benign (0.2684); Rare (popmax 0.13%, amr).

How common is EPOP p.Pro16Leu (c.47C>T) in the general population?

EPOP p.Pro16Leu (c.47C>T) is rare (popmax 0.13%, amr) (gnomAD).

What do computational predictors say about EPOP p.Pro16Leu (c.47C>T)?

AlphaMissense predicts likely benign (score 0.2684) — an in-silico prediction, not a clinical call.

EPOP p.Pro16Leu

c.47C>T · rs935636952 · VCV3089789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2684 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.13%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2684	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -7.96	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 9.2	GERP 1.4, phastCons 1
Overall
CADD	27.1	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

Grpmax group 0.13% Admixed American · 66/50,864 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0955%

Overall 0.00461% 71/1,539,528 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.13%	771
Remaining individualsnot grpmax-eligible	0.00501%	19,943
African / African-American	0.00137%	72,844
European (non-Finnish)	8.73e-05%	1,145,470

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: EPOP
Protein: p.Pro16Leu
Coding: c.47C>T
MANE Select: NM_001130677
dbSNP: rs935636952
Type: single nucleotide variant
Location: chr17:38674449 (GRCh38)
Gene constraint: LOEUF 1.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.12 · 2 PDB
Residue 16: the 'disordered' region

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

Similar variants

EPOP p.Arg282Pro Uncertain significance ★ ⚠ same type
EPOP p.Leu164Phe Uncertain significance ★ ⚠ same type
EPOP p.Pro84Leu 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/epop-p-pro16leu (accessed [today's date]).

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