Is CLCC1 p.Lys52Arg (c.155A>G) pathogenic?

CLCC1 p.Lys52Arg (c.155A>G) is classified Uncertain significance in CLCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-12). AlphaMissense: likely benign (0.0816); Very rare (popmax 0.0027%, afr).

How common is CLCC1 p.Lys52Arg (c.155A>G) in the general population?

CLCC1 p.Lys52Arg (c.155A>G) is very rare (popmax 0.0027%, afr) (gnomAD).

What do computational predictors say about CLCC1 p.Lys52Arg (c.155A>G)?

AlphaMissense predicts likely benign (score 0.0816) — an in-silico prediction, not a clinical call.

CLCC1 p.Lys52Arg

c.155A>G · rs1654980142 · VCV2074732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0816 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0027%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0816	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -6.36	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 2.8	GERP 1.7, phastCons 0.9
Regional constraint	o/e 0.82	unconstrained · MANE · 16 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	19.47	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 0.0027% African / African-American · 2/74,210 alleles

Filtering AF 0.000447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000251% 4/1,594,094 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0027%	37,105
European (non-Finnish)	0.000171%	585,257

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.Lys52Arg
Coding: c.155A>G
MANE Select: NM_001377458
dbSNP: rs1654980142
Type: single nucleotide variant
Location: chr1:108949896 (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

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CLCC1 p.Arg208His Uncertain significance ★★ ⚠ same type
CLCC1 p.Arg377Trp Uncertain significance ★★ ⚠ same type
CLCC1 p.Arg381Trp Uncertain significance ★★ ⚠ same type
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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-lys52arg (accessed [today's date]).

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