Is CLCC1 p.Tyr76= (c.228T>C) pathogenic?

CLCC1 p.Tyr76= (c.228T>C) is classified Likely benign in CLCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). Very rare (popmax 0.000441%, nfe).

How common is CLCC1 p.Tyr76= (c.228T>C) in the general population?

CLCC1 p.Tyr76= (c.228T>C) is very rare (popmax 0.000441%, nfe) (gnomAD).

CLCC1 p.Tyr76=

c.228T>C · rs1571058373 · VCV2174070

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000441%, 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 0.15	GERP -3.5, phastCons 0.21
Overall
CADD	6.928	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000441% European (non-Finnish) · 5/1,132,622 alleles

Filtering AF 0.000129% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.4e-05%

Overall 0.000361% 5/1,385,588 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: CLCC1
Protein: p.Tyr76=
Coding: c.228T>C
MANE Select: NM_001377458
dbSNP: rs1571058373
Type: single nucleotide variant
Location: chr1:108949823 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.13

Full CLCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLCC1 p.Tyr76Asn Uncertain significance ★ ⚠ same residue
CLCC1 p.Tyr76Asp Uncertain significance ★ ⚠ same residue
CLCC1 p.Tyr76Cys Uncertain significance ★ ⚠ same residue
CLCC1 p.Tyr76_Lys77insTer Uncertain significance ★ same residue
CLCC1 p.Asp25Glu Pathogenic/Likely pathogenic ★★ ⚠ same type
CLCC1 p.Ala245Thr Uncertain significance ★★ ⚠ same type
CLCC1 p.Ala522Thr Uncertain significance ★★ ⚠ same type
CLCC1 p.Arg208His 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/clcc1-p-tyr76 (accessed [today's date]).

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