Is EVC p.Ala701= (c.2103G>A) pathogenic?

EVC p.Ala701= (c.2103G>A) is classified Likely benign in EVC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-18). Very rare (popmax 0.00758%, amr); Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC p.Ala701= (c.2103G>A)?

EVC p.Ala701= (c.2103G>A) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Ala701= (c.2103G>A) in the general population?

EVC p.Ala701= (c.2103G>A) is very rare (popmax 0.00758%, amr) (gnomAD).

EVC p.Ala701=

c.2103G>A · rs766383397 · VCV740679

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00758%, amr)

Conditions

acrofacial dysostosis, Weyers type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.4
Overall
CADD	0.006	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00758% Admixed American · 4/52,762 alleles

Filtering AF 0.00257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.0016% 25/1,564,270 alleles · very rare exomes 22/1,412,058 · genomes 3/152,212 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00758%	13,191
East Asian	0.00476%	20,997
African / African-American	0.00407%	24,577
Remaining individualsnot grpmax-eligible	0.00165%	60,534
European (non-Finnish)	0.00121%	82,538
South Asian	0.00118%	84,960

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.Ala701=
Coding: c.2103G>A
MANE Select: NM_153717
dbSNP: rs766383397
Type: single nucleotide variant
Location: chr4:5798591 (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

acrofacial dysostosis, Weyers type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ellis-van Creveld syndrome

Similar variants

EVC p.Ala701Val Conflicting classifications of pathogenicity ★ ⚠ same residue
EVC p.Ala701Ser Uncertain significance ★ ⚠ same residue
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

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-ala701 (accessed [today's date]).

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