Is CLINT1 p.Ser430Phe (c.1289C>T) pathogenic?

CLINT1 p.Ser430Phe (c.1289C>T) is classified Uncertain significance in CLINT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.2542); Very rare (popmax 0.00267%, afr).

How common is CLINT1 p.Ser430Phe (c.1289C>T) in the general population?

CLINT1 p.Ser430Phe (c.1289C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CLINT1 p.Ser430Phe (c.1289C>T)?

AlphaMissense predicts likely benign (score 0.2542) — an in-silico prediction, not a clinical call.

CLINT1 p.Ser430Phe

c.1289C>T · VCV4229897

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2542 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2542	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -10.87	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Pangolin	Δ0.27	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 18 kb · p 0.079 · regional, not allelic
Overall
CADD	25.9	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 0.00267% African / African-American · 2/74,920 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000991% 16/1,613,860 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,232
African / African-Americangrpmax	0.00267%	37,460
European (non-Finnish)	0.00102%	98,325

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser430Phe
Coding: c.1289C>T
MANE Select: NM_014666
Type: single nucleotide variant
Location: chr5:157791794 (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-ser430phe (accessed [today's date]).

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