Is DPYS p.Met1Ile (c.3G>A) pathogenic?

DPYS p.Met1Ile (c.3G>A) is classified Uncertain significance in DPYS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). Ultra-rare (popmax 0.0303%, amr).

How common is DPYS p.Met1Ile (c.3G>A) in the general population?

DPYS p.Met1Ile (c.3G>A) is ultra-rare (popmax 0.0303%, amr) (gnomAD).

DPYS p.Met1Ile

c.3G>A · rs1032598870 · VCV1904077

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0303%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.611	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 0.32, phastCons 1
Overall
CADD	19.72	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0303% Admixed American · 14/46,236 alleles

Filtering AF 0.0183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00121% 18/1,488,304 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0303%	3,303
African / African-American	0.00437%	22,906
European (non-Finnish)	8.88e-05%	1,125,707

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: DPYS
Protein: p.Met1Ile
Coding: c.3G>A
MANE Select: NM_001385
dbSNP: rs1032598870
Type: single nucleotide variant
Location: chr8:104466918 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.00 · 1 PDB

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

Similar variants

DPYS c.424-1G>A Pathogenic/Likely pathogenic ★★ same type
DPYS p.Arg302Gln Likely pathogenic ★★ same type
DPYS p.Arg302Ter Pathogenic/Likely pathogenic ★★ same type
DPYS p.Arg465Ter Pathogenic ★★ same type
DPYS p.Arg475Ter Pathogenic/Likely pathogenic ★★ same type
DPYS p.Arg490Cys Pathogenic/Likely pathogenic ★★ same type
DPYS p.Arg490His Pathogenic/Likely pathogenic ★★ same type
DPYS p.Gln190Ter 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/dpys-p-met1ile (accessed [today's date]).

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