Is EDC3 p.Val278Phe (c.832G>T) pathogenic?

EDC3 p.Val278Phe (c.832G>T) is classified Uncertain significance in EDC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-02). AlphaMissense: likely pathogenic (0.6274); Ultra-rare (popmax 0.011%, sas).

How common is EDC3 p.Val278Phe (c.832G>T) in the general population?

EDC3 p.Val278Phe (c.832G>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about EDC3 p.Val278Phe (c.832G>T)?

AlphaMissense predicts likely pathogenic (score 0.6274) — an in-silico prediction, not a clinical call.

EDC3 p.Val278Phe

c.832G>T · rs745568902 · VCV2263071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6274 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6274	likely pathogenic
REVEL	0.353	indeterminate
SaProt	LLR -8.39	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 23 kb · p 1.7e-10 · regional, not allelic
Overall
CADD	29.0	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 0.011% South Asian · 10/91,092 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.000682% 11/1,614,056 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,109
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: EDC3
Protein: p.Val278Phe
Coding: c.832G>T
MANE Select: NM_025083
dbSNP: rs745568902
Type: single nucleotide variant
Location: chr15:74640608 (GRCh38)
Gene constraint: LOEUF 0.656 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 77.04 · 6 PDB
Residue 278: a β-strand; the 'required for interaction with ddx6' region

Full EDC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EDC3 p.Val278Ile Uncertain significance ★ ⚠ same residue
EDC3 p.Arg260Trp Uncertain significance ★★ ⚠ same type
EDC3 p.Thr273= Benign ★★ same type
EDC3 c.821-2A>C Uncertain significance ★ same type
EDC3 p.Ala129Thr Uncertain significance ★ ⚠ same type
EDC3 p.Ala172Pro Uncertain significance ★ ⚠ same type
EDC3 p.Ala312Thr Uncertain significance ★ ⚠ same type
EDC3 p.Arg232His 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/edc3-p-val278phe (accessed [today's date]).

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