Is CLINT1 p.Ala621Val (c.1862C>T) pathogenic?

CLINT1 p.Ala621Val (c.1862C>T) is classified Uncertain significance in CLINT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: ambiguous (0.4433); Very rare (popmax 0.00246%, nfe).

How common is CLINT1 p.Ala621Val (c.1862C>T) in the general population?

CLINT1 p.Ala621Val (c.1862C>T) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about CLINT1 p.Ala621Val (c.1862C>T)?

AlphaMissense predicts ambiguous (score 0.4433) — an in-silico prediction, not a clinical call.

CLINT1 p.Ala621Val

c.1862C>T · VCV4654396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4433 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4433	ambiguous
REVEL	0.142	moderately benign-leaning
SaProt	LLR -10.62	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 18 kb · p 0.079 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 0.00246% European (non-Finnish) · 29/1,179,204 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00186% 30/1,612,806 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,662
African / African-American	0.00134%	74,874

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.Ala621Val
Coding: c.1862C>T
MANE Select: NM_014666
Type: single nucleotide variant
Location: chr5:157787662 (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 p.Ala621Thr Uncertain significance ★ ⚠ same residue
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

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-ala621val (accessed [today's date]).

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