Is CLINT1 p.Met596Val (c.1786A>G) pathogenic?

CLINT1 p.Met596Val (c.1786A>G) is classified Uncertain significance in CLINT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.0639); Ultra-rare (popmax 0.015%, amr).

How common is CLINT1 p.Met596Val (c.1786A>G) in the general population?

CLINT1 p.Met596Val (c.1786A>G) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about CLINT1 p.Met596Val (c.1786A>G)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

CLINT1 p.Met596Val

c.1786A>G · VCV4003667

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.117	moderately benign-leaning
SaProt	LLR -8.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -3.7, phastCons 0.041
Regional constraint	o/e 0.91	unconstrained · MANE · 18 kb · p 0.079 · regional, not allelic
Overall
CADD	12.66	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 0.015% Admixed American · 9/59,998 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.000805% 13/1,613,910 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,666
European (non-Finnish)	0.000339%	294,972

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: CLINT1
Protein: p.Met596Val
Coding: c.1786A>G
MANE Select: NM_014666
Type: single nucleotide variant
Location: chr5:157787738 (GRCh38)
Gene constraint: LOEUF 0.419 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.15 · 3 PDB

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-met596val (accessed [today's date]).

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