Is DHPS p.Ala68= (c.204C>T) pathogenic?

DHPS p.Ala68= (c.204C>T) is classified Benign in DHPS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-09). Common (popmax 12.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with DHPS-related disorder.

What condition is associated with DHPS p.Ala68= (c.204C>T)?

DHPS p.Ala68= (c.204C>T) is associated with DHPS-related disorder (ClinVar).

DHPS p.Ala68=

Q: How common is DHPS p.Ala68= (c.204C>T) in the general population?

DHPS p.Ala68= (c.204C>T) is common (popmax 12.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.204C>T · rs11541391 · VCV3056608

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 12.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

DHPS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -2, phastCons 1
Overall
CADD	11.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.4% African / African-American · 9,312/75,034 alleles

Filtering AF 12.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.1%

Overall 0.677% 10,928/1,614,210 alleles · common exomes 5,576/1,461,864 · genomes 5,352/152,346 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.4%	8
Remaining individualsnot grpmax-eligible	0.974%	103
Admixed American	0.956%	105
Middle Eastern	0.907%	110
South Asian	0.034%	2,938
European (non-Finnish)	0.0289%	3,461
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,922
East Asian	0.00223%	44,884

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.Ala68=
Coding: c.204C>T
MANE Select: NM_001930
dbSNP: rs11541391
Type: single nucleotide variant
Location: chr19:12681563 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.95 · 89 PDB
Residue 68: an α-helix

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

Disease context

DHPS-related disorder

Similar variants

DHPS p.Asn173Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
DHPS c.207+462G>A Benign same condition
DHPS p.Arg7= Likely benign same condition
DHPS p.Pro145= Likely benign same condition
DHPS p.Ser204= Benign same condition
DHPS p.Ser219= Benign same condition
DHPS p.Glu71Lys Uncertain significance ★★ ⚠ same type
DHPS p.Gly162Arg Uncertain significance ★★ ⚠ 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-ala68 (accessed [today's date]).

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