Is EVC p.Pro30Thr (c.88C>A) pathogenic?

EVC p.Pro30Thr (c.88C>A) is classified Uncertain significance in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-31). AlphaMissense: likely benign (0.2764); No allele count reported in gnomAD v4.1 (AN 1,064,338); Associated with Inborn genetic diseases.

What condition is associated with EVC p.Pro30Thr (c.88C>A)?

EVC p.Pro30Thr (c.88C>A) is associated with Inborn genetic diseases (ClinVar).

How common is EVC p.Pro30Thr (c.88C>A) in the general population?

EVC p.Pro30Thr (c.88C>A) is no allele count reported in gnomAD v4.1 (AN 1,064,338) (gnomAD).

What do computational predictors say about EVC p.Pro30Thr (c.88C>A)?

AlphaMissense predicts likely benign (score 0.2764) — an in-silico prediction, not a clinical call.

EVC p.Pro30Thr

c.88C>A · rs991390298 · VCV2274562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2764 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,064,338)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2764	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -3.68	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 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	18.44	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

No allele count reported in gnomAD v4.1 (AN 1,064,338). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EVC
Protein: p.Pro30Thr
Coding: c.88C>A
MANE Select: NM_153717
dbSNP: rs991390298
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.Pro30Ala 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-pro30thr (accessed [today's date]).

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