Is CLINT1 p.Ser316Pro (c.946T>C) pathogenic?

CLINT1 p.Ser316Pro (c.946T>C) is classified Uncertain significance in CLINT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). AlphaMissense: likely benign (0.0773); Very rare (popmax 0.00458%, eas).

How common is CLINT1 p.Ser316Pro (c.946T>C) in the general population?

CLINT1 p.Ser316Pro (c.946T>C) is very rare (popmax 0.00458%, eas) (gnomAD).

What do computational predictors say about CLINT1 p.Ser316Pro (c.946T>C)?

AlphaMissense predicts likely benign (score 0.0773) — an in-silico prediction, not a clinical call.

CLINT1 p.Ser316Pro

c.946T>C · VCV3267740

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0773 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00458%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0773	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -6.94	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 9.4	GERP -0.59, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 18 kb · p 0.079 · regional, not allelic
Overall
CADD	22.3	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 0.00458% East Asian · 2/43,680 alleles

Filtering AF 0.000759% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000284%

Overall 0.000214% 3/1,401,628 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00458%	21,840
Remaining individualsnot grpmax-eligible	0.00168%	59,550

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.Ser316Pro
Coding: c.946T>C
MANE Select: NM_014666
Type: single nucleotide variant
Location: chr5:157803716 (GRCh38)
Gene constraint: LOEUF 0.419 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.15 · 3 PDB
Residue 316: the 'disordered' 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-ser316pro (accessed [today's date]).

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