Is CDIPT p.Tyr27Cys (c.80A>G) pathogenic?

CDIPT p.Tyr27Cys (c.80A>G) is classified Uncertain significance in CDIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: likely benign (0.1024); Very rare (popmax 0.00446%, eas).

How common is CDIPT p.Tyr27Cys (c.80A>G) in the general population?

CDIPT p.Tyr27Cys (c.80A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CDIPT p.Tyr27Cys (c.80A>G)?

AlphaMissense predicts likely benign (score 0.1024) — an in-silico prediction, not a clinical call.

CDIPT p.Tyr27Cys

c.80A>G · rs1300496152 · VCV2221116

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1024 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1024	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -10.71	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 3,665 bp · p 0.068 · regional, not allelic
Overall
CADD	27.9	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 0.00446% East Asian · 2/44,848 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000479% 7/1,461,746 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,424
South Asian	0.0022%	45,533
Admixed American	0.00167%	59,988
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	8.48e-05%	1,179,889

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: CDIPT
Protein: p.Tyr27Cys
Coding: c.80A>G
MANE Select: NM_006319
dbSNP: rs1300496152
Type: single nucleotide variant
Location: chr16:29862684 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.02

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

Similar variants

CDIPT p.Ala140Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala146Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala206Val Uncertain significance ★ ⚠ same type
CDIPT p.Ala22Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala48Thr Uncertain significance ★ ⚠ same type
CDIPT p.Ala84Val Uncertain significance ★ ⚠ same type
CDIPT p.Arg115Gln Uncertain significance ★ ⚠ same type
CDIPT p.Arg138Lys 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/cdipt-p-tyr27cys (accessed [today's date]).

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