Is EVC p.Arg760Gln (c.2279G>A) pathogenic?

EVC p.Arg760Gln (c.2279G>A) is classified Benign/Likely benign in EVC (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-05-11). AlphaMissense: likely benign (0.0825); Common (popmax 6.86%, eas) — too common for a highly-penetrant pathogenic allele; Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC p.Arg760Gln (c.2279G>A)?

EVC p.Arg760Gln (c.2279G>A) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

What do computational predictors say about EVC p.Arg760Gln (c.2279G>A)?

AlphaMissense predicts likely benign (score 0.0825) — an in-silico prediction, not a clinical call.

EVC p.Arg760Gln

Q: How common is EVC p.Arg760Gln (c.2279G>A) in the general population?

EVC p.Arg760Gln (c.2279G>A) is common (popmax 6.86%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2279G>A · rs2279252 · VCV262771

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0825 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.86%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

acrofacial dysostosis, Weyers type

Computational evidence

Protein change
AlphaMissense	0.0825	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -6.03	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 3.8	GERP 0.71, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	20.8	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 6.86% East Asian · 3,076/44,858 alleles

Filtering AF 6.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.57%

Overall 1.72% 27,631/1,611,026 alleles · common exomes 25,215/1,458,730 · genomes 2,416/152,296 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	6.86%	15
Amishnot grpmax-eligible	5.93%	17
South Asian	4.55%	22
Admixed American	3.54%	28
Finnishnot grpmax-eligible	3.01%	33
Middle Eastern	2.04%	49
Remaining individualsnot grpmax-eligible	1.78%	56
European (non-Finnish)	1.24%	80
Ashkenazi Jewishnot grpmax-eligible	0.855%	117
African / African-American	0.299%	335

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.Arg760Gln
Coding: c.2279G>A
MANE Select: NM_153717
dbSNP: rs2279252
Type: single nucleotide variant
Location: chr4:5798767 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49
Residue 760: a UniProt-annotated variant site (in)

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.Arg760Trp Conflicting classifications of pathogenicity ★ ⚠ 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
EVC c.1886+5G>T 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-arg760gln (accessed [today's date]).

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