Is CCT5 p.Met1Arg (c.2T>G) pathogenic?

CCT5 p.Met1Arg (c.2T>G) is classified Uncertain significance in CCT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-13). Very rare (popmax 0.000424%, nfe).

How common is CCT5 p.Met1Arg (c.2T>G) in the general population?

CCT5 p.Met1Arg (c.2T>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

CCT5 p.Met1Arg

c.2T>G · rs1355388433 · VCV618555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function in a LoF-intolerant gene
REVEL	0.414	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.30	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 2.6, phastCons 1
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,028 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00041% 6/1,461,730 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)grpmax	0.000424%	236,005

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CCT5
Protein: p.Met1Arg
Coding: c.2T>G
MANE Select: NM_012073
dbSNP: rs1355388433
Type: single nucleotide variant
Location: chr5:10250342 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.34 · 75 PDB

Full CCT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT5 p.Met1Val Uncertain significance ★★ same residue
CCT5 p.Met1Leu Uncertain significance ★ same residue
CCT5 c.531-3C>T Uncertain significance ★★ same type
CCT5 c.*1126T>A Uncertain significance ★★ same type
CCT5 c.*567G>A Uncertain significance ★★ same type
CCT5 p.Ala246Val Uncertain significance ★★ ⚠ same type
CCT5 p.Ala41Gly Uncertain significance ★★ ⚠ same type
CCT5 p.Ala424Ser 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/cct5-p-met1arg (accessed [today's date]).

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