Is TYMP p.Ser65= (c.195C>T) pathogenic?

TYMP p.Ser65= (c.195C>T) is classified Likely benign in TYMP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Very rare (popmax 0.00534%, afr).

How common is TYMP p.Ser65= (c.195C>T) in the general population?

TYMP p.Ser65= (c.195C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

TYMP p.Ser65=

c.195C>T · rs142027728 · VCV750917

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

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 -6.4	GERP -3.7
Overall
CADD	0.712	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,948 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00093% 15/1,612,754 alleles · very rare exomes 13/1,460,500 · genomes 2/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,737
European (non-Finnish)	0.000932%	107,265

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.Ser65=
Coding: c.195C>T
MANE Select: NM_001953
dbSNP: rs142027728
Type: single nucleotide variant
Location: chr22:50529515 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.82 · 4 PDB

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

Similar variants

TYMP p.Ser65Arg Uncertain significance ★★ ⚠ same residue
TYMP p.Ser65Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
TYMP p.Ser65Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
TYMP c.1301-1G>A Likely pathogenic ★★ same type
TYMP c.214+1G>T Likely pathogenic ★★ same type
TYMP c.417+1G>A Pathogenic ★★ same type
TYMP c.418-1G>A Likely pathogenic ★★ same type
TYMP c.646+1G>A Pathogenic/Likely pathogenic ★★ 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/tymp-p-ser65 (accessed [today's date]).

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