Is EVC p.Ala114Ser (c.340G>T) pathogenic?

EVC p.Ala114Ser (c.340G>T) is classified Uncertain significance in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.3296); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with EVC p.Ala114Ser (c.340G>T)?

EVC p.Ala114Ser (c.340G>T) is associated with Inborn genetic diseases (ClinVar).

How common is EVC p.Ala114Ser (c.340G>T) in the general population?

EVC p.Ala114Ser (c.340G>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about EVC p.Ala114Ser (c.340G>T)?

AlphaMissense predicts likely benign (score 0.3296) — an in-silico prediction, not a clinical call.

EVC p.Ala114Ser

c.340G>T · rs756208272 · VCV2615560

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3296 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3296	likely benign
REVEL	0.526	indeterminate
SaProt	LLR -5.44	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 1.8, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	24.1	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 0.0011% South Asian · 1/91,076 alleles

Overall 0.000124% 2/1,613,980 alleles · very rare exomes 2/1,461,890 · genomes 0/152,090 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,076
European (non-Finnish)	8.47e-05%	1,180,016

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.Ala114Ser
Coding: c.340G>T
MANE Select: NM_153717
dbSNP: rs756208272
Type: single nucleotide variant
Location: chr4:5729346 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49
Residue 114: a UniProt-annotated variant site (in)

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.Ala114Thr Uncertain significance ★★ ⚠ same residue
EVC p.Ala114Val Benign/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
EVC p.Arg622Gln 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-ala114ser (accessed [today's date]).

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