Is CCT5 p.Ser3Phe (c.8C>T) pathogenic?

CCT5 p.Ser3Phe (c.8C>T) is classified Uncertain significance in CCT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: ambiguous (0.4926); Very rare (popmax 0.000593%, nfe).

How common is CCT5 p.Ser3Phe (c.8C>T) in the general population?

CCT5 p.Ser3Phe (c.8C>T) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about CCT5 p.Ser3Phe (c.8C>T)?

AlphaMissense predicts ambiguous (score 0.4926) — an in-silico prediction, not a clinical call.

CCT5 p.Ser3Phe

c.8C>T · VCV3829282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4926 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4926	ambiguous
REVEL	0.152	moderately benign-leaning
SaProt	LLR -8.01	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 5,706 bp · p 0.00087 · regional, not allelic
Overall
CADD	25.9	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 0.000593% European (non-Finnish) · 7/1,180,030 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000547% 8/1,461,758 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	63,910
European (non-Finnish)grpmax	0.000593%	168,576

Finnish 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.Ser3Phe
Coding: c.8C>T
MANE Select: NM_012073
Type: single nucleotide variant
Location: chr5:10250348 (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 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
CCT5 p.Arg142Cys Uncertain significance ★★ ⚠ same type
CCT5 p.Arg400Leu 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-ser3phe (accessed [today's date]).

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