Is EDC4 p.Phe1118Leu (c.3354C>G) pathogenic?

EDC4 p.Phe1118Leu (c.3354C>G) is classified Uncertain significance in EDC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-05). AlphaMissense: likely pathogenic (0.9878); Absent from gnomAD v4.1.

How common is EDC4 p.Phe1118Leu (c.3354C>G) in the general population?

EDC4 p.Phe1118Leu (c.3354C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDC4 p.Phe1118Leu (c.3354C>G)?

AlphaMissense predicts likely pathogenic (score 0.9878) — an in-silico prediction, not a clinical call.

EDC4 p.Phe1118Leu

c.3354C>G · rs2544355773 · VCV2532969

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9878 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9878	likely pathogenic · top 6% in EDC4
REVEL	0.265	benign-leaning
SaProt	LLR -5.13	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 1.8	GERP 0.83, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 3,251 bp · p 6.4e-17 · regional, not allelic
Overall
CADD	23.3	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: EDC4
Protein: p.Phe1118Leu
Coding: c.3354C>G
MANE Select: NM_014329
dbSNP: rs2544355773
Type: single nucleotide variant
Location: chr16:67882506 (GRCh38)
Gene constraint: LOEUF 0.494 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 63.18

Full EDC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EDC4 p.Gly309= Benign ★★ same type
EDC4 p.Ala1030Val Uncertain significance ★ ⚠ same type
EDC4 p.Ala1036Thr Uncertain significance ★ ⚠ same type
EDC4 p.Ala1076Thr Uncertain significance ★ ⚠ same type
EDC4 p.Ala1117Asp Uncertain significance ★ ⚠ same type
EDC4 p.Ala1284Val Uncertain significance ★ ⚠ same type
EDC4 p.Ala26Gly Uncertain significance ★ ⚠ same type
EDC4 p.Ala315Val 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/edc4-p-phe1118leu (accessed [today's date]).

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