Is MTAP p.Thr8= (c.24C>T) pathogenic?

MTAP p.Thr8= (c.24C>T) is classified Likely benign in MTAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). Ultra-rare (popmax 0.0166%, mid).

How common is MTAP p.Thr8= (c.24C>T) in the general population?

MTAP p.Thr8= (c.24C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

MTAP p.Thr8=

c.24C>T · VCV4902756

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.62	GERP -3.1
Overall
CADD	8.229	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,032 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.00116% 17/1,461,186 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,032
Remaining individualsnot grpmax-eligible	0.00641%	15,612
European (non-Finnish)	0.00102%	98,325

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: MTAP
Protein: p.Thr8=
Coding: c.24C>T
MANE Select: NM_002451
Type: single nucleotide variant
Location: chr9:21802772 (GRCh38)
Gene constraint: LOEUF 1.489 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 92.99 · 18 PDB

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

Similar variants

MTAP c.*1453C>T Uncertain significance ★★ same type
MTAP p.Gln75Arg Uncertain significance ★★ ⚠ same type
MTAP c.120+279C>T Benign ★★ same type
MTAP c.121-10T>C Benign ★★ same type
MTAP c.121-140G>A Benign ★★ same type
MTAP c.121-185A>G Benign ★★ same type
MTAP c.121-67A>G Benign ★★ same type
MTAP c.121-76T>C Benign ★★ 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/mtap-p-thr8 (accessed [today's date]).

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