Is CPVL p.Asp101Val (c.302A>T) pathogenic?

CPVL p.Asp101Val (c.302A>T) is classified Uncertain significance in CPVL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.079); Very rare (popmax 6.84e-05%).

How common is CPVL p.Asp101Val (c.302A>T) in the general population?

CPVL p.Asp101Val (c.302A>T) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about CPVL p.Asp101Val (c.302A>T)?

AlphaMissense predicts likely benign (score 0.079) — an in-silico prediction, not a clinical call.

CPVL p.Asp101Val

c.302A>T · rs1584249841 · VCV2250279

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.079 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.079	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -3.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.38	GERP -3.3
Regional constraint	o/e 0.92	unconstrained · MANE · 125 kb · p 0.072 · regional, not allelic
Overall
CADD	4.246	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 6.84e-05%

Overall 6.84e-05% 1/1,461,576 alleles · very rare

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: CPVL
Protein: p.Asp101Val
Coding: c.302A>T
MANE Select: NM_031311
dbSNP: rs1584249841
Type: single nucleotide variant
Location: chr7:29096204 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.55

Full CPVL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPVL p.Arg464Gln Likely benign ★★ ⚠ same type
CPVL p.Met5Thr Likely benign ★★ same type
CPVL p.Ala234Val Uncertain significance ★ ⚠ same type
CPVL p.Ala341Thr Uncertain significance ★ ⚠ same type
CPVL p.Arg136Cys Uncertain significance ★ ⚠ same type
CPVL p.Arg136His Uncertain significance ★ ⚠ same type
CPVL p.Arg136Pro Uncertain significance ★ ⚠ same type
CPVL p.Arg177Pro Uncertain significance ★ ⚠ same type

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/cpvl-p-asp101val (accessed [today's date]).

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