Is EREG p.Pro152Leu (c.455C>T) pathogenic?

EREG p.Pro152Leu (c.455C>T) is classified Uncertain significance in EREG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). AlphaMissense: likely benign (0.1054); Ultra-rare (popmax 0.012%, afr).

How common is EREG p.Pro152Leu (c.455C>T) in the general population?

EREG p.Pro152Leu (c.455C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about EREG p.Pro152Leu (c.455C>T)?

AlphaMissense predicts likely benign (score 0.1054) — an in-silico prediction, not a clinical call.

EREG p.Pro152Leu

c.455C>T · VCV3510050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1054 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1054	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -4.83	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 2.7	phastCons 0.03
Regional constraint	o/e 1.10	unconstrained · MANE · 19 kb · p 0.16 · regional, not allelic
Overall
CADD	15.83	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 0.012% African / African-American · 9/74,740 alleles

Filtering AF 0.00625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00469%

Overall 0.00062% 10/1,611,780 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,304
European (non-Finnish)	8.48e-05%	1,178,573

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: EREG
Protein: p.Pro152Leu
Coding: c.455C>T
MANE Select: NM_001432
Type: single nucleotide variant
Location: chr4:74384753 (GRCh38)
Gene constraint: LOEUF 1.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.40 · 8 PDB

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

Similar variants

EREG p.Arg147Gln Benign ★★ ⚠ same type
EREG p.Arg145Gly Uncertain significance ★ ⚠ same type
EREG p.Arg59His Uncertain significance ★ ⚠ same type
EREG p.Asp56Gly Uncertain significance ★ ⚠ same type
EREG p.Gln62His Uncertain significance ★ ⚠ same type
EREG p.Gly13Arg Uncertain significance ★ ⚠ same type
EREG p.Gly74Ser Uncertain significance ★ ⚠ same type
EREG p.His111Leu 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/ereg-p-pro152leu (accessed [today's date]).

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