Is CCNT2 p.Arg255Gln (c.764G>A) pathogenic?

CCNT2 p.Arg255Gln (c.764G>A) is classified Uncertain significance in CCNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-08). AlphaMissense: ambiguous (0.5027); Ultra-rare (popmax 0.0166%, mid).

How common is CCNT2 p.Arg255Gln (c.764G>A) in the general population?

CCNT2 p.Arg255Gln (c.764G>A) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about CCNT2 p.Arg255Gln (c.764G>A)?

AlphaMissense predicts ambiguous (score 0.5027) — an in-silico prediction, not a clinical call.

CCNT2 p.Arg255Gln

c.764G>A · VCV3487513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5027 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5027	ambiguous
REVEL	0.24	benign-leaning
SaProt	LLR -8.62	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 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 34 kb · p 2.5e-16 · regional, not allelic
Overall
CADD	34.0	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 0.0166% Middle Eastern · 1/6,036 alleles

Filtering AF 0.000368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000138%

Overall 0.000482% 7/1,452,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,036
Finnishnot grpmax-eligible	0.00313%	31,968
South Asian	0.00221%	45,168
European (non-Finnish)	0.00017%	587,009

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: CCNT2
Protein: p.Arg255Gln
Coding: c.764G>A
MANE Select: NM_058241
Type: single nucleotide variant
Location: chr2:134952701 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.93 · 1 PDB
Residue 255: the 'interaction with mdfic and mdfi' region; the 'interaction with polr2a' region; an α-helix

Full CCNT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNT2 p.Arg255Ter Uncertain significance ★ same residue
CCNT2 p.Asp717Asn Uncertain significance ★★ ⚠ same type
CCNT2 p.Ala335Ser Uncertain significance ★ ⚠ same type
CCNT2 p.Ala458Thr Uncertain significance ★ ⚠ same type
CCNT2 p.Asn208Asp Uncertain significance ★ ⚠ same type
CCNT2 p.Asn700Ser Uncertain significance ★ ⚠ same type
CCNT2 p.Asn729Ser Uncertain significance ★ ⚠ same type
CCNT2 p.Asp119Glu 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/ccnt2-p-arg255gln (accessed [today's date]).

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