Is CLECL1 p.Ala8Val (c.23C>T) pathogenic?

CLECL1 p.Ala8Val (c.23C>T) is classified Uncertain significance in CLECL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.2311); Ultra-rare (popmax 0.0293%, afr).

How common is CLECL1 p.Ala8Val (c.23C>T) in the general population?

CLECL1 p.Ala8Val (c.23C>T) is ultra-rare (popmax 0.0293%, afr) (gnomAD).

What do computational predictors say about CLECL1 p.Ala8Val (c.23C>T)?

AlphaMissense predicts likely benign (score 0.2311) — an in-silico prediction, not a clinical call.

CLECL1 p.Ala8Val

c.23C>T · rs139676111 · VCV3145726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2311 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0293%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2311	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.75	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 5.4	GERP 0.72, phastCons 1
Overall
CADD	13.94	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A86V vs ClinVar A8V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0293% African / African-American · 22/75,058 alleles

Filtering AF 0.0198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00136% 22/1,614,166 alleles · ultra-rare

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: CLECL1
Protein: p.Ala8Val
Coding: c.23C>T
dbSNP: rs139676111
Type: single nucleotide variant
Location: chr12:9733008 (GRCh38)
Structure: AlphaFold pLDDT 53.91

Full CLECL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLECL1 c.4-35C>A Uncertain significance ★ ⚠ same type
CLECL1 c.-27G>A Uncertain significance ★ ⚠ same type
CLECL1 c.-5G>C Uncertain significance ★ ⚠ same type
CLECL1 n.231T>C Uncertain significance ★ ⚠ same type
CLECL1 n.303G>A Uncertain significance ★ ⚠ same type
CLECL1 n.307G>A Uncertain significance ★ ⚠ same type
CLECL1 n.373A>C Uncertain significance ★ ⚠ same type
CLECL1 n.52A>G 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/clecl1-p-ala8val (accessed [today's date]).

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