Is CLCC1 p.Pro439Ser (c.1315C>T) pathogenic?

CLCC1 p.Pro439Ser (c.1315C>T) is classified Uncertain significance in CLCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.1308); Absent from gnomAD v4.1.

How common is CLCC1 p.Pro439Ser (c.1315C>T) in the general population?

CLCC1 p.Pro439Ser (c.1315C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLCC1 p.Pro439Ser (c.1315C>T)?

AlphaMissense predicts likely benign (score 0.1308) — an in-silico prediction, not a clinical call.

CLCC1 p.Pro439Ser

c.1315C>T · VCV3493297

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1308 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1308	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -6.67	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 9.8	GERP 0.69, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 16 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	23.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLCC1
Protein: p.Pro439Ser
Coding: c.1315C>T
MANE Select: NM_001377458
Type: single nucleotide variant
Location: chr1:108937145 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.13
Residue 439: a UniProt-annotated variant site (found in a patient with sporadic als)

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

Similar variants

CLCC1 p.Pro439Arg Uncertain significance ★ ⚠ same residue
CLCC1 p.Pro439Leu 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
CLCC1 p.Arg377Trp Uncertain significance ★★ ⚠ same type
CLCC1 p.Arg381Trp 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-pro439ser (accessed [today's date]).

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