Is DPYD p.Thr552Ala (c.1654A>G) pathogenic?

DPYD p.Thr552Ala (c.1654A>G) is classified Uncertain significance in DPYD (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-16). AlphaMissense: likely benign (0.1492); Very rare (popmax 0.00659%, sas).

How common is DPYD p.Thr552Ala (c.1654A>G) in the general population?

DPYD p.Thr552Ala (c.1654A>G) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about DPYD p.Thr552Ala (c.1654A>G)?

AlphaMissense predicts likely benign (score 0.1492) — an in-silico prediction, not a clinical call.

DPYD p.Thr552Ala

c.1654A>G · rs771648776 · VCV585801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1492 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1492	likely benign
REVEL	0.346	indeterminate
SaProt	LLR -12.45	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 2.1, phastCons 0.92
Regional constraint	o/e 1.04	unconstrained · MANE · 842 kb · p 0.18 · regional, not allelic
Overall
CADD	21.7	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 0.00659% South Asian · 6/91,050 alleles

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

Overall 0.000685% 10/1,460,862 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,175
Admixed American	0.00167%	59,814
Remaining individualsnot grpmax-eligible	0.0016%	62,426
European (non-Finnish)	0.00017%	589,623

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: DPYD
Protein: p.Thr552Ala
Coding: c.1654A>G
MANE Select: NM_000110
dbSNP: rs771648776
Type: single nucleotide variant
Location: chr1:97515812 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.23

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

Similar variants

DPYD c.1340-2A>C Likely pathogenic ★★ same type
DPYD c.1905+1G>C Pathogenic/Likely pathogenic ★★ same type
DPYD c.233+1G>T Likely pathogenic ★★ same type
DPYD c.2622+1G>A Likely pathogenic ★★ same type
DPYD c.2767-1G>A Likely pathogenic ★★ same type
DPYD c.680+1G>T Likely pathogenic ★★ same type
DPYD p.Arg21Ter Pathogenic/Likely pathogenic ★★ same type
DPYD p.Arg561Ter 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/dpyd-p-thr552ala (accessed [today's date]).

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