Is EVC p.Pro30Ala (c.88C>G) pathogenic?

EVC p.Pro30Ala (c.88C>G) is classified Uncertain significance in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: likely benign (0.1591); Very rare (popmax 0.00171%, afr); Associated with Inborn genetic diseases.

What condition is associated with EVC p.Pro30Ala (c.88C>G)?

EVC p.Pro30Ala (c.88C>G) is associated with Inborn genetic diseases (ClinVar).

How common is EVC p.Pro30Ala (c.88C>G) in the general population?

EVC p.Pro30Ala (c.88C>G) is very rare (popmax 0.00171%, afr) (gnomAD).

What do computational predictors say about EVC p.Pro30Ala (c.88C>G)?

AlphaMissense predicts likely benign (score 0.1591) — an in-silico prediction, not a clinical call.

EVC p.Pro30Ala

c.88C>G · VCV3276647

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1591 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00171%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1591	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -0.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.6	GERP 1.2, phastCons 0.24
Regional constraint	o/e 1.12	unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	16.49	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 0.00171% African / African-American · 1/58,600 alleles

Filtering AF 0.000329% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000212%

Overall 0.000752% 8/1,064,228 alleles · very rare exomes 6/916,430 · genomes 2/147,798 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00171%	58,600
European (non-Finnish)	0.000792%	126,267

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.Pro30Ala
Coding: c.88C>G
MANE Select: NM_153717
Type: single nucleotide variant
Location: chr4:5711468 (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

EVC p.Pro30Thr Uncertain significance ★ ⚠ same residue
EVC p.Pro30Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
EVC p.Pro30= Likely benign ★ same residue
EVC p.Ala20Pro Uncertain significance ★★ ⚠ same condition
EVC p.Ala365Asp Uncertain significance ★★ ⚠ same condition
EVC p.Ala365Thr Uncertain significance ★★ ⚠ same condition
EVC p.Arg340Gln Uncertain significance ★★ ⚠ same condition
EVC p.Arg438Trp 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-pro30ala (accessed [today's date]).

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