Is EVC2 p.Ala172Thr (c.514G>A) pathogenic?

EVC2 p.Ala172Thr (c.514G>A) is classified Uncertain significance in EVC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: ambiguous (0.3557); Very rare (popmax 0.00401%, afr); Associated with Inborn genetic diseases.

What condition is associated with EVC2 p.Ala172Thr (c.514G>A)?

EVC2 p.Ala172Thr (c.514G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EVC2 p.Ala172Thr (c.514G>A) in the general population?

EVC2 p.Ala172Thr (c.514G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about EVC2 p.Ala172Thr (c.514G>A)?

AlphaMissense predicts ambiguous (score 0.3557) — an in-silico prediction, not a clinical call.

EVC2 p.Ala172Thr

c.514G>A · VCV3510671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3557 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3557	ambiguous
REVEL	0.432	indeterminate
SaProt	LLR -10.82	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5	GERP 1.6, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 146 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	23.5	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 0.00401% African / African-American · 3/74,900 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,613,226 alleles · very rare exomes 1/1,461,046 · genomes 2/152,180 · joint denominator

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: EVC2
Protein: p.Ala172Thr
Coding: c.514G>A
MANE Select: NM_147127
Type: single nucleotide variant
Location: chr4:5691270 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.33

Full EVC2 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

EVC2 p.Ala172= Likely benign ★ same residue
EVC2 p.Gln1089Ter Pathogenic ★★ same condition
EVC2 p.Ala1132Val Uncertain significance ★★ ⚠ same condition
EVC2 p.Ala1150Asp Uncertain significance ★★ ⚠ same condition
EVC2 p.Ala1260Val Uncertain significance ★★ ⚠ same condition
EVC2 p.Ala618Thr Uncertain significance ★★ ⚠ same condition
EVC2 p.Ala703Val Uncertain significance ★★ ⚠ same condition
EVC2 p.Arg1140Cys 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/evc2-p-ala172thr (accessed [today's date]).

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