Is EVC p.Glu439Val (c.1316A>T) pathogenic?

EVC p.Glu439Val (c.1316A>T) is classified Uncertain significance in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-22). AlphaMissense: likely benign (0.1923); Very rare (popmax 0.00347%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EVC p.Glu439Val (c.1316A>T)?

EVC p.Glu439Val (c.1316A>T) is associated with Inborn genetic diseases (ClinVar).

How common is EVC p.Glu439Val (c.1316A>T) in the general population?

EVC p.Glu439Val (c.1316A>T) is very rare (popmax 0.00347%, nfe) (gnomAD).

What do computational predictors say about EVC p.Glu439Val (c.1316A>T)?

AlphaMissense predicts likely benign (score 0.1923) — an in-silico prediction, not a clinical call.

EVC p.Glu439Val

c.1316A>T · VCV3846580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1923 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00347%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1923	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -7.96	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 7.8	GERP 0.36, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	25.0	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 0.00347% European (non-Finnish) · 41/1,179,932 alleles

Filtering AF 0.00259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.00254% 41/1,613,772 alleles · very rare exomes 40/1,461,686 · genomes 1/152,086 · joint denominator

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: EVC
Protein: p.Glu439Val
Coding: c.1316A>T
MANE Select: NM_153717
Type: single nucleotide variant
Location: chr4:5753785 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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EVC p.Arg438Trp Uncertain significance ★★ ⚠ same condition
EVC p.Arg622Gln Uncertain significance ★★ ⚠ same condition
EVC p.Arg647Trp Uncertain significance ★★ ⚠ same condition
EVC p.Arg702Gly Uncertain significance ★★ ⚠ same condition

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/evc-p-glu439val (accessed [today's date]).

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