Is C2CD2L p.Ala550Val (c.1649C>T) pathogenic?

C2CD2L p.Ala550Val (c.1649C>T) is classified Uncertain significance in C2CD2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-22). AlphaMissense: likely benign (0.2915); Very rare (popmax 0.00508%, nfe).

How common is C2CD2L p.Ala550Val (c.1649C>T) in the general population?

C2CD2L p.Ala550Val (c.1649C>T) is very rare (popmax 0.00508%, nfe) (gnomAD).

What do computational predictors say about C2CD2L p.Ala550Val (c.1649C>T)?

AlphaMissense predicts likely benign (score 0.2915) — an in-silico prediction, not a clinical call.

C2CD2L p.Ala550Val

c.1649C>T · VCV3826274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2915 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00508%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2915	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -7.62	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 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 8,511 bp · p 2.1e-05 · regional, not allelic
Overall
CADD	23.7	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 0.00508% European (non-Finnish) · 60/1,180,030 alleles

Filtering AF 0.00402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00362%

Overall 0.00409% 66/1,613,986 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00508%	19,667
Admixed American	0.005%	19,998
Remaining individualsnot grpmax-eligible	0.0032%	31,240
South Asian	0.0011%	91,078

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: C2CD2L
Protein: p.Ala550Val
Coding: c.1649C>T
MANE Select: NM_001290474
Type: single nucleotide variant
Location: chr11:119114105 (GRCh38)
Gene constraint: LOEUF 0.494 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 64.75 · 1 PDB
Residue 550: the 'association with the cell membrane' region

Full C2CD2L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD2L c.451-8G>A Benign ★★ same type
C2CD2L p.Ala14Thr Uncertain significance ★ ⚠ same type
C2CD2L p.Ala173Thr Uncertain significance ★ ⚠ same type
C2CD2L p.Ala245Ser Uncertain significance ★ ⚠ same type
C2CD2L p.Ala245Thr Uncertain significance ★ ⚠ same type
C2CD2L p.Ala326Val Uncertain significance ★ ⚠ same type
C2CD2L p.Ala512Val Uncertain significance ★ ⚠ same type
C2CD2L p.Ala524Thr 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/c2cd2l-p-ala550val (accessed [today's date]).

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