Is CLVS2 p.Leu58Val (c.172T>G) pathogenic?

CLVS2 p.Leu58Val (c.172T>G) is classified Uncertain significance in CLVS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely pathogenic (0.7937); Absent from gnomAD v4.1.

How common is CLVS2 p.Leu58Val (c.172T>G) in the general population?

CLVS2 p.Leu58Val (c.172T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLVS2 p.Leu58Val (c.172T>G)?

AlphaMissense predicts likely pathogenic (score 0.7937) — an in-silico prediction, not a clinical call.

CLVS2 p.Leu58Val

c.172T>G · VCV3834260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7937 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7937	likely pathogenic
REVEL	0.901	moderately pathogenic-leaning
SaProt	LLR -9.43	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.65, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 58 kb · p 1.2e-11 · regional, not allelic
Overall
CADD	23.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLVS2
Protein: p.Leu58Val
Coding: c.172T>G
MANE Select: NM_001010852
Type: single nucleotide variant
Location: chr6:122997949 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.15

Full CLVS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLVS2 p.Ala139Gly Uncertain significance ★ ⚠ same type
CLVS2 p.Ala146Thr Uncertain significance ★ ⚠ same type
CLVS2 p.Arg138Gly Uncertain significance ★ ⚠ same type
CLVS2 p.Arg215Trp Uncertain significance ★ ⚠ same type
CLVS2 p.Arg48Cys Uncertain significance ★ ⚠ same type
CLVS2 p.Asp272Gly Uncertain significance ★ ⚠ same type
CLVS2 p.Glu19Gln Uncertain significance ★ same type
CLVS2 p.Glu316Gly 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/clvs2-p-leu58val (accessed [today's date]).

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