Is CCT4 p.Ser202Asn (c.605G>A) pathogenic?

CCT4 p.Ser202Asn (c.605G>A) is classified Uncertain significance in CCT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-20). AlphaMissense: likely benign (0.1369); Ultra-rare (popmax 0.0317%, nfe).

How common is CCT4 p.Ser202Asn (c.605G>A) in the general population?

CCT4 p.Ser202Asn (c.605G>A) is ultra-rare (popmax 0.0317%, nfe) (gnomAD).

What do computational predictors say about CCT4 p.Ser202Asn (c.605G>A)?

AlphaMissense predicts likely benign (score 0.1369) — an in-silico prediction, not a clinical call.

CCT4 p.Ser202Asn

c.605G>A · rs368053865 · VCV2349005

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1369 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1369	likely benign
REVEL	0.453	indeterminate
SaProt	LLR -4.00	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 15 kb · p 0.04 · regional, not allelic
Overall
CADD	20.7	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 0.0317% European (non-Finnish) · 374/1,178,638 alleles

Filtering AF 0.029% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.0239% 386/1,611,906 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0317%	3,151
Remaining individualsnot grpmax-eligible	0.00801%	12,483
African / African-American	0.00668%	14,963
Finnishnot grpmax-eligible	0.00313%	31,968

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: CCT4
Protein: p.Ser202Asn
Coding: c.605G>A
MANE Select: NM_006430
dbSNP: rs368053865
Type: single nucleotide variant
Location: chr2:61877432 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 90.05 · 72 PDB
Residue 202: a modified residue (phosphoserine)

Full CCT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT4 p.Ser202Gly Uncertain significance ★ ⚠ same residue
CCT4 p.Ala113Gly Uncertain significance ★ ⚠ same type
CCT4 p.Ala113Val Uncertain significance ★ ⚠ same type
CCT4 p.Ala308Val Uncertain significance ★ ⚠ same type
CCT4 p.Ala408Ser Uncertain significance ★ ⚠ same type
CCT4 p.Ala41Thr Uncertain significance ★ ⚠ same type
CCT4 p.Ala518Ser Uncertain significance ★ ⚠ same type
CCT4 p.Arg274Gln 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/cct4-p-ser202asn (accessed [today's date]).

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