Is EVC p.Glu370Val (c.1109A>T) pathogenic?

EVC p.Glu370Val (c.1109A>T) is classified Uncertain significance in EVC (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-27). AlphaMissense: ambiguous (0.3716); Very rare (popmax 0.0089%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EVC p.Glu370Val (c.1109A>T)?

EVC p.Glu370Val (c.1109A>T) is associated with Inborn genetic diseases, Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Glu370Val (c.1109A>T) in the general population?

EVC p.Glu370Val (c.1109A>T) is very rare (popmax 0.0089%, nfe) (gnomAD).

What do computational predictors say about EVC p.Glu370Val (c.1109A>T)?

AlphaMissense predicts ambiguous (score 0.3716) — an in-silico prediction, not a clinical call.

EVC p.Glu370Val

c.1109A>T · rs778032532 · VCV990323

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0089%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3716	ambiguous
REVEL	0.362	indeterminate
SaProt	LLR -7.33	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	23.8	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 0.0089% European (non-Finnish) · 105/1,180,022 alleles

Filtering AF 0.00749% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.007%

Overall 0.00682% 110/1,614,070 alleles · very rare exomes 107/1,461,876 · genomes 3/152,194 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0089%	11,238
Remaining individualsnot grpmax-eligible	0.008%	12,498

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.Glu370Val
Coding: c.1109A>T
MANE Select: NM_153717
dbSNP: rs778032532
Type: single nucleotide variant
Location: chr4:5752846 (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

Also linked: Ellis-van Creveld syndrome

Similar variants

EVC c.1098+1G>A Pathogenic/Likely pathogenic ★★ same condition
EVC c.175-2A>G Pathogenic/Likely pathogenic ★★ same condition
EVC c.1777-1G>A Pathogenic/Likely pathogenic ★★ same condition
EVC c.1777-2A>G Pathogenic/Likely pathogenic ★★ same condition
EVC c.1886+1G>C Likely pathogenic ★★ same condition
EVC c.1886+5G>A Pathogenic ★★ same condition
EVC c.1886+5G>T Pathogenic/Likely pathogenic ★★ same condition
EVC c.2304+2T>C Pathogenic/Likely pathogenic ★★ 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-glu370val (accessed [today's date]).

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