Is C2CD5 p.Thr150Met (c.449C>T) pathogenic?

C2CD5 p.Thr150Met (c.449C>T) is classified Uncertain significance in C2CD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.1626); Ultra-rare (popmax 0.0443%, amr).

How common is C2CD5 p.Thr150Met (c.449C>T) in the general population?

C2CD5 p.Thr150Met (c.449C>T) is ultra-rare (popmax 0.0443%, amr) (gnomAD).

What do computational predictors say about C2CD5 p.Thr150Met (c.449C>T)?

AlphaMissense predicts likely benign (score 0.1626) — an in-silico prediction, not a clinical call.

C2CD5 p.Thr150Met

c.449C>T · VCV4647274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1626 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0443%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1626	likely benign
REVEL	0.385	indeterminate
SaProt	LLR -12.51	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.51 · evaluated, not missing
Pangolin	Δ0.31	gain · loss 0.19 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 1,114 bp · p 0.67 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0443% Admixed American · 26/58,654 alleles

Filtering AF 0.031% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0266%

Overall 0.00274% 44/1,605,928 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0443%	2,256
Remaining individualsnot grpmax-eligible	0.00161%	62,254
European (non-Finnish)	0.00145%	69,178

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: C2CD5
Protein: p.Thr150Met
Coding: c.449C>T
MANE Select: NM_001286176
Type: single nucleotide variant
Location: chr12:22524624 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.34

Full C2CD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD5 p.Ala21Thr Uncertain significance ★ ⚠ same type
C2CD5 p.Ala242Thr Uncertain significance ★ ⚠ same type
C2CD5 p.Ala252Thr Uncertain significance ★ ⚠ same type
C2CD5 p.Ala342Val Uncertain significance ★ ⚠ same type
C2CD5 p.Ala355Thr Uncertain significance ★ ⚠ same type
C2CD5 p.Ala405Val Uncertain significance ★ ⚠ same type
C2CD5 p.Ala433Val Uncertain significance ★ ⚠ same type
C2CD5 p.Ala527Thr 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/c2cd5-p-thr150met (accessed [today's date]).

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