Is EVC p.Ser286Leu (c.857C>T) pathogenic?

EVC p.Ser286Leu (c.857C>T) is classified Likely benign in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely benign (0.0584); Very rare (popmax 0.00668%, afr); Associated with Inborn genetic diseases.

What condition is associated with EVC p.Ser286Leu (c.857C>T)?

EVC p.Ser286Leu (c.857C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EVC p.Ser286Leu (c.857C>T) in the general population?

EVC p.Ser286Leu (c.857C>T) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about EVC p.Ser286Leu (c.857C>T)?

AlphaMissense predicts likely benign (score 0.0584) — an in-silico prediction, not a clinical call.

EVC p.Ser286Leu

c.857C>T · VCV4251524

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0584 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0584	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.06	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 0.01	GERP -1.1, phastCons 0.005
Regional constraint	o/e 1.12	unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	13.14	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 0.00668% African / African-American · 5/74,822 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00409% 66/1,613,664 alleles · very rare exomes 63/1,461,760 · genomes 3/151,904 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,964
European (non-Finnish)	0.00466%	21,452
South Asian	0.00439%	22,767
East Asian	0.00223%	44,890
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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.Ser286Leu
Coding: c.857C>T
MANE Select: NM_153717
Type: single nucleotide variant
Location: chr4:5745259 (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.Ser286Trp Uncertain significance ★★ ⚠ same residue
EVC p.Ser286Ter Likely pathogenic ★ same residue
EVC p.Ser286= 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-ser286leu (accessed [today's date]).

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