Is CTC1 p.Met1Val (c.1A>G) pathogenic?

CTC1 p.Met1Val (c.1A>G) is classified Pathogenic in CTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-30). Very rare (popmax 0.00176%, amr); Associated with dyskeratosis congenita.

What condition is associated with CTC1 p.Met1Val (c.1A>G)?

CTC1 p.Met1Val (c.1A>G) is associated with dyskeratosis congenita (ClinVar).

How common is CTC1 p.Met1Val (c.1A>G) in the general population?

CTC1 p.Met1Val (c.1A>G) is very rare (popmax 0.00176%, amr) (gnomAD).

How is Dyskeratosis congenita inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CTC1 p.Met1Val

c.1A>G · rs779499831 · VCV2202444

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00176%, amr)

Conditions

dyskeratosis congenita

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.636	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7	GERP 2.4, phastCons 1
Overall
CADD	21.1	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 0.00176% Admixed American · 1/56,690 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000214% 3/1,399,376 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00176%	56,690
European (non-Finnish)	0.000175%	570,090

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: CTC1
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_012393 · reported on NM_025099
dbSNP: rs779499831
Type: single nucleotide variant
Location: chr17:8248036 (GRCh38)

Full CTC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dyskeratosis congenita — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dyskeratosis congenita (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

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/ctc1-p-met1val (accessed [today's date]).

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