Is TYMP p.Pro480= (c.1440G>A) pathogenic?

TYMP p.Pro480= (c.1440G>A) is classified Likely benign in TYMP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). Very rare (popmax 0.00659%, sas).

How common is TYMP p.Pro480= (c.1440G>A) in the general population?

TYMP p.Pro480= (c.1440G>A) is very rare (popmax 0.00659%, sas) (gnomAD).

TYMP p.Pro480=

c.1440G>A · rs768543479 · VCV1133777

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.83	GERP -3, phastCons 0.99
Overall
CADD	11.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,018 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00143% 23/1,610,642 alleles · very rare exomes 22/1,458,404 · genomes 1/152,238 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,170
Remaining individualsnot grpmax-eligible	0.00161%	62,268
African / African-American	0.00134%	74,870
European (non-Finnish)	0.00127%	78,598

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: TYMP
Protein: p.Pro480=
Coding: c.1440G>A
MANE Select: NM_001953
dbSNP: rs768543479
Type: single nucleotide variant
Location: chr22:50525779 (GRCh38)

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

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/tymp-p-pro480 (accessed [today's date]).

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