Is EDRF1 p.Leu460Phe (c.1380G>C) pathogenic?

EDRF1 p.Leu460Phe (c.1380G>C) is classified Uncertain significance in EDRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-31). AlphaMissense: likely pathogenic (0.6085); Absent from gnomAD v4.1.

How common is EDRF1 p.Leu460Phe (c.1380G>C) in the general population?

EDRF1 p.Leu460Phe (c.1380G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDRF1 p.Leu460Phe (c.1380G>C)?

AlphaMissense predicts likely pathogenic (score 0.6085) — an in-silico prediction, not a clinical call.

EDRF1 p.Leu460Phe

c.1380G>C · rs2493581850 · VCV2480149

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6085 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6085	likely pathogenic
REVEL	0.237	benign-leaning
SaProt	LLR -9.17	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.8
Regional constraint	o/e 0.77	unconstrained · MANE · 38 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	15.66	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

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: EDRF1
Protein: p.Leu460Phe
Coding: c.1380G>C
MANE Select: NM_001202438
dbSNP: rs2493581850
Type: single nucleotide variant
Location: chr10:125733738 (GRCh38)
Gene constraint: LOEUF 0.53 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 76.41

Full EDRF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EDRF1 p.Leu159= Benign ★★ same type
EDRF1 p.Thr480= Benign ★★ same type
EDRF1 p.Thr731= Benign ★★ same type
EDRF1 p.Ala1137Ser Uncertain significance ★ ⚠ same type
EDRF1 p.Ala1210Thr Uncertain significance ★ ⚠ same type
EDRF1 p.Ala1228Thr Uncertain significance ★ ⚠ same type
EDRF1 p.Ala203Thr Uncertain significance ★ ⚠ same type
EDRF1 p.Ala226Ser 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/edrf1-p-leu460phe (accessed [today's date]).

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