Is EPN3 p.Phe307Ser (c.920T>C) pathogenic?

EPN3 p.Phe307Ser (c.920T>C) is classified Uncertain significance in EPN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: ambiguous (0.4834); Very rare (popmax 0.00814%, nfe).

How common is EPN3 p.Phe307Ser (c.920T>C) in the general population?

EPN3 p.Phe307Ser (c.920T>C) is very rare (popmax 0.00814%, nfe) (gnomAD).

What do computational predictors say about EPN3 p.Phe307Ser (c.920T>C)?

AlphaMissense predicts ambiguous (score 0.4834) — an in-silico prediction, not a clinical call.

EPN3 p.Phe307Ser

c.920T>C · VCV3845550

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00814%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4834	ambiguous
REVEL	0.207	benign-leaning
SaProt	LLR -6.68	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.3, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 5,597 bp · p 0.012 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00814% European (non-Finnish) · 96/1,179,962 alleles

Filtering AF 0.00681% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00651% 105/1,612,640 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00814%	12,291
African / African-American	0.00534%	18,728
Admixed American	0.00333%	30,000
Remaining individualsnot grpmax-eligible	0.0032%	31,236
South Asian	0.0011%	91,082

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: EPN3
Protein: p.Phe307Ser
Coding: c.920T>C
MANE Select: NM_017957
Type: single nucleotide variant
Location: chr17:50540275 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.01

Full EPN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPN3 p.Ala244Val Uncertain significance ★ ⚠ same type
EPN3 p.Ala267Thr Uncertain significance ★ ⚠ same type
EPN3 p.Ala270Gly Uncertain significance ★ ⚠ same type
EPN3 p.Ala334Ser Uncertain significance ★ ⚠ same type
EPN3 p.Ala334Thr Uncertain significance ★ ⚠ same type
EPN3 p.Ala390Val Uncertain significance ★ ⚠ same type
EPN3 p.Ala492Val Uncertain significance ★ ⚠ same type
EPN3 p.Ala541Glu 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/epn3-p-phe307ser (accessed [today's date]).

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