Is CLEC4M p.Ala122= (c.366A>G) pathogenic?

CLEC4M p.Ala122= (c.366A>G) is classified Likely benign in CLEC4M (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). Very rare (popmax 8.48e-05%, nfe).

How common is CLEC4M p.Ala122= (c.366A>G) in the general population?

CLEC4M p.Ala122= (c.366A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CLEC4M p.Ala122=

c.366A>G · rs750548064 · VCV2555048

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2
Overall
CADD	3.777	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,028 alleles

Overall 6.85e-05% 1/1,460,686 alleles · very 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: CLEC4M
Protein: p.Ala122=
Coding: c.366A>G
MANE Select: NM_014257
dbSNP: rs750548064
Type: single nucleotide variant
Location: chr19:7765789 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 7 PDB
Residue 122: the '7 x approximate tandem repeats' region; an α-helix

Full CLEC4M gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC4M p.Ala145Val Uncertain significance ★ ⚠ same type
CLEC4M p.Ala237Thr Uncertain significance ★ ⚠ same type
CLEC4M p.Ala295Val Uncertain significance ★ ⚠ same type
CLEC4M p.Ala393Val Uncertain significance ★ ⚠ same type
CLEC4M p.Ala394Gly Uncertain significance ★ ⚠ same type
CLEC4M p.Ala62Gly Uncertain significance ★ ⚠ same type
CLEC4M p.Arg141Trp Uncertain significance ★ ⚠ same type
CLEC4M p.Arg353Trp 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/clec4m-p-ala122 (accessed [today's date]).

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