Is DHPS p.Thr88Ser (c.262A>T) pathogenic?

DHPS p.Thr88Ser (c.262A>T) is classified Uncertain significance in DHPS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: likely benign (0.0732); Ultra-rare (popmax 0.01%, amr).

How common is DHPS p.Thr88Ser (c.262A>T) in the general population?

DHPS p.Thr88Ser (c.262A>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about DHPS p.Thr88Ser (c.262A>T)?

AlphaMissense predicts likely benign (score 0.0732) — an in-silico prediction, not a clinical call.

DHPS p.Thr88Ser

c.262A>T · rs145365284 · VCV3082028

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0732 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0732	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -5.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 5,925 bp · p 0.58 · regional, not allelic
Overall
CADD	19.37	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 0.01% Admixed American · 6/59,998 alleles

Filtering AF 0.00656% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00608%

Overall 0.00626% 101/1,614,068 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,000
European (non-Finnish)	0.00788%	12,688
Remaining individualsnot grpmax-eligible	0.0032%	31,254

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: DHPS
Protein: p.Thr88Ser
Coding: c.262A>T
MANE Select: NM_001930
dbSNP: rs145365284
Type: single nucleotide variant
Location: chr19:12680271 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.95 · 89 PDB
Residue 88: an α-helix

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

Similar variants

DHPS p.Thr88= Likely benign ★★ same residue
DHPS p.Glu71Lys Uncertain significance ★★ ⚠ same type
DHPS p.Gly162Arg Uncertain significance ★★ ⚠ same type
DHPS p.Met124Leu Uncertain significance ★★ ⚠ same type
DHPS c.784+8G>T Likely benign ★★ same type
DHPS p.Lys358= Likely benign ★★ same type
DHPS c.785-1G>C Likely pathogenic ★ same type
DHPS p.Gln194Ter 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/dhps-p-thr88ser (accessed [today's date]).

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