Is CLINT1 p.Leu89Val (c.265C>G) pathogenic?

CLINT1 p.Leu89Val (c.265C>G) is classified Uncertain significance in CLINT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). AlphaMissense: likely pathogenic (0.9177); Absent from gnomAD v4.1.

How common is CLINT1 p.Leu89Val (c.265C>G) in the general population?

CLINT1 p.Leu89Val (c.265C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLINT1 p.Leu89Val (c.265C>G)?

AlphaMissense predicts likely pathogenic (score 0.9177) — an in-silico prediction, not a clinical call.

CLINT1 p.Leu89Val

c.265C>G · VCV3267741

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9177 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9177	likely pathogenic
REVEL	0.578	indeterminate
SaProt	LLR -11.35	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 53 kb · p 3e-11 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: CLINT1
Protein: p.Leu89Val
Coding: c.265C>G
MANE Select: NM_014666
Type: single nucleotide variant
Location: chr5:157814272 (GRCh38)
Gene constraint: LOEUF 0.419 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.15 · 3 PDB
Residue 89: the enth domain; an α-helix

Full CLINT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLINT1 c.1381-12C>G Uncertain significance ★ same type
CLINT1 c.1381-15C>A Uncertain significance ★ same type
CLINT1 c.1381-16T>A Uncertain significance ★ same type
CLINT1 c.1381-53C>T Uncertain significance ★ same type
CLINT1 c.1381-8A>G Uncertain significance ★ same type
CLINT1 p.Ala354Ser Uncertain significance ★ ⚠ same type
CLINT1 p.Ala381Asp Uncertain significance ★ ⚠ same type
CLINT1 p.Ala400Val 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/clint1-p-leu89val (accessed [today's date]).

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