Is CLEC1A p.Ala42Thr (c.124G>A) pathogenic?

CLEC1A p.Ala42Thr (c.124G>A) is classified Likely benign in CLEC1A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). AlphaMissense: likely benign (0.0651); Ultra-rare (popmax 0.0293%, afr).

How common is CLEC1A p.Ala42Thr (c.124G>A) in the general population?

CLEC1A p.Ala42Thr (c.124G>A) is ultra-rare (popmax 0.0293%, afr) (gnomAD).

What do computational predictors say about CLEC1A p.Ala42Thr (c.124G>A)?

AlphaMissense predicts likely benign (score 0.0651) — an in-silico prediction, not a clinical call.

CLEC1A p.Ala42Thr

c.124G>A · rs200997403 · VCV2461534

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0651 · 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	0.0651	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -6.44	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 0.52	GERP -3.2, phastCons 0.015
Regional constraint	o/e 1.13	unconstrained · MANE · 28 kb · p 0.014 · regional, not allelic
Overall
CADD	10.65	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 0.0293% African / African-American · 22/75,022 alleles

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

Overall 0.00204% 33/1,613,744 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0293%	3,410
Remaining individualsnot grpmax-eligible	0.016%	6,249
European (non-Finnish)	8.48e-05%	1,179,714

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: CLEC1A
Protein: p.Ala42Thr
Coding: c.124G>A
MANE Select: NM_016511
dbSNP: rs200997403
Type: single nucleotide variant
Location: chr12:10089214 (GRCh38)
Gene constraint: LOEUF 1.529 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.51
Residue 42: the 'disordered' region

Full CLEC1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC1A p.Gly26Ala Benign ★★ same type
CLEC1A p.His32Arg Likely benign ★★ same type
CLEC1A p.Ala238Asp Uncertain significance ★ same type
CLEC1A p.Ala261Val Uncertain significance ★ ⚠ same type
CLEC1A p.Arg254His Uncertain significance ★ ⚠ same type
CLEC1A p.Arg31Trp Uncertain significance ★ ⚠ same type
CLEC1A p.Arg36Trp Uncertain significance ★ ⚠ same type
CLEC1A p.Asp10Glu 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/clec1a-p-ala42thr (accessed [today's date]).

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