Is EVC p.Arg873His (c.2618G>A) pathogenic?

EVC p.Arg873His (c.2618G>A) is classified Uncertain significance in EVC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-21). AlphaMissense: likely benign (0.1813); Very rare (popmax 0.0077%, sas); Associated with Inborn genetic diseases.

What condition is associated with EVC p.Arg873His (c.2618G>A)?

EVC p.Arg873His (c.2618G>A) is associated with Inborn genetic diseases, acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Arg873His (c.2618G>A) in the general population?

EVC p.Arg873His (c.2618G>A) is very rare (popmax 0.0077%, sas) (gnomAD).

What do computational predictors say about EVC p.Arg873His (c.2618G>A)?

AlphaMissense predicts likely benign (score 0.1813) — an in-silico prediction, not a clinical call.

EVC p.Arg873His

c.2618G>A · rs767972554 · VCV2386600

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1813 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0077%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1813	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -6.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	26.9	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 0.0077% South Asian · 7/90,952 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00304% 49/1,611,872 alleles · very rare exomes 45/1,461,792 · genomes 4/150,080 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0077%	12,993
East Asian	0.00446%	22,410
European (non-Finnish)	0.00322%	31,037
Admixed American	0.00167%	59,776
African / African-American	0.00135%	74,218

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.Arg873His
Coding: c.2618G>A
MANE Select: NM_153717
dbSNP: rs767972554
Type: single nucleotide variant
Location: chr4:5808257 (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: acrofacial dysostosis, Weyers type Ellis-van Creveld syndrome

Similar variants

EVC p.Arg873Cys Uncertain significance ★ ⚠ same residue
EVC p.Arg873= Likely benign ★ same residue
EVC p.Arg873Leu 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

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-arg873his (accessed [today's date]).

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