Is TYMP p.Arg265Pro (c.794G>C) pathogenic?

TYMP p.Arg265Pro (c.794G>C) is classified Uncertain significance in TYMP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-12). AlphaMissense: likely benign (0.1907); Very rare (popmax 8.72e-05%, nfe).

How common is TYMP p.Arg265Pro (c.794G>C) in the general population?

TYMP p.Arg265Pro (c.794G>C) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

What do computational predictors say about TYMP p.Arg265Pro (c.794G>C)?

AlphaMissense predicts likely benign (score 0.1907) — an in-silico prediction, not a clinical call.

TYMP p.Arg265Pro

c.794G>C · rs2069401085 · VCV2155471

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1907 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1907	likely benign
REVEL	0.387	indeterminate
SaProt	LLR -3.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP -0.62, phastCons 0.14
Regional constraint	o/e 1.24	unconstrained · MANE · 3,936 bp · p 9.1e-10 · regional, not allelic
Overall
CADD	16.04	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.72e-05% European (non-Finnish) · 1/1,147,382 alleles

Overall 6.49e-05% 1/1,539,782 alleles · very rare exomes 1/1,387,410 · genomes 0/152,372 · joint denominator

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.Arg265Pro
Coding: c.794G>C
MANE Select: NM_001953
dbSNP: rs2069401085
Type: single nucleotide variant
Location: chr22:50526710 (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 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
TYMP c.647-1G>A Pathogenic/Likely pathogenic ★★ same type
TYMP p.Ala216Val Likely pathogenic ★★ same type
TYMP p.Asp114Asn 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-arg265pro (accessed [today's date]).

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