Is TYMP p.Ala201Asp (c.602C>A) pathogenic?

TYMP p.Ala201Asp (c.602C>A) is classified Conflicting classifications of pathogenicity in TYMP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-31). AlphaMissense: likely pathogenic (0.5741); Ultra-rare (popmax 0.0571%, sas).

How common is TYMP p.Ala201Asp (c.602C>A) in the general population?

TYMP p.Ala201Asp (c.602C>A) is ultra-rare (popmax 0.0571%, sas) (gnomAD).

What do computational predictors say about TYMP p.Ala201Asp (c.602C>A)?

AlphaMissense predicts likely pathogenic (score 0.5741) — an in-silico prediction, not a clinical call.

TYMP p.Ala201Asp

c.602C>A · rs550422674 · VCV1112209

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5741 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0571%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5741	likely pathogenic
REVEL	0.614	indeterminate
SaProt	LLR -12.65	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.62, phastCons 0.72
Regional constraint	o/e 1.24	unconstrained · MANE · 3,936 bp · p 9.1e-10 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0571% South Asian · 52/91,082 alleles

Filtering AF 0.0447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0403%

Overall 0.00384% 62/1,613,930 alleles · ultra-rare exomes 60/1,461,658 · genomes 2/152,272 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0571%	1,752
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0064%	15,625
European (non-Finnish)	0.000424%	236,005

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.Ala201Asp
Coding: c.602C>A
MANE Select: NM_001953
dbSNP: rs550422674
Type: single nucleotide variant
Location: chr22:50527632 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.82 · 4 PDB
Residue 201: an α-helix

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-ala201asp (accessed [today's date]).

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