Is CLINT1 p.Phe347Val (c.1039T>G) pathogenic?

CLINT1 p.Phe347Val (c.1039T>G) is classified Uncertain significance in CLINT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely pathogenic (0.7281); Ultra-rare (popmax 0.0169%, eas).

How common is CLINT1 p.Phe347Val (c.1039T>G) in the general population?

CLINT1 p.Phe347Val (c.1039T>G) is ultra-rare (popmax 0.0169%, eas) (gnomAD).

What do computational predictors say about CLINT1 p.Phe347Val (c.1039T>G)?

AlphaMissense predicts likely pathogenic (score 0.7281) — an in-silico prediction, not a clinical call.

CLINT1 p.Phe347Val

c.1039T>G · VCV4654397

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7281 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7281	likely pathogenic
REVEL	0.355	indeterminate
SaProt	LLR -10.35	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 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 18 kb · p 0.079 · regional, not allelic
Overall
CADD	25.8	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

Grpmax group 0.0169% East Asian · 7/41,364 alleles

Filtering AF 0.0079% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0056%

Overall 0.000579% 9/1,555,268 alleles · ultra-rare exomes 7/1,403,048 · genomes 2/152,220 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0169%	5,909
Remaining individualsnot grpmax-eligible	0.00166%	60,310
European (non-Finnish)	8.7e-05%	1,148,910

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.Phe347Val
Coding: c.1039T>G
MANE Select: NM_014666
Type: single nucleotide variant
Location: chr5:157794946 (GRCh38)
Gene constraint: LOEUF 0.419 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.15 · 3 PDB
Residue 347: the 'interaction with ap1g1, ap1g2 and gga2' region

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-phe347val (accessed [today's date]).

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