Is POR p.Val331= (c.993C>A) pathogenic?

POR p.Val331= (c.993C>A) is classified Likely benign in POR (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-24). Very rare (popmax 0.00133%, afr); Associated with congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency.

How common is POR p.Val331= (c.993C>A) in the general population?

POR p.Val331= (c.993C>A) is very rare (popmax 0.00133%, afr) (gnomAD).

POR p.Val331=

Q: What condition is associated with POR p.Val331= (c.993C>A)?

POR p.Val331= (c.993C>A) is associated with congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency (ClinVar).

Q: How is Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.993C>A · VCV4747873

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.014	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.064	phastCons 0.86
Overall
CADD	6.143	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,946 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,612,308 alleles · very rare exomes 1/1,460,084 · genomes 2/152,224 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,946
European (non-Finnish)	0.00017%	589,866

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: POR
Protein: p.Val331=
Coding: c.993C>A
MANE Select: NM_001395413
Type: single nucleotide variant
Location: chr7:75983792 (GRCh38)
Gene constraint: LOEUF 0.887 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.29 · 14 PDB
Residue 331: the fad-binding fr-type domain; an α-helix

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

Disease context

congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

POR c.1240-2A>G Likely pathogenic ★★ same condition
POR c.179+2T>C Likely pathogenic ★★ same condition
POR c.723-2A>T Pathogenic ★★ same condition
POR c.821+1G>A Pathogenic/Likely pathogenic ★★ same condition
POR p.Arg220Ter Pathogenic ★★ same condition
POR p.Arg454His Pathogenic/Likely pathogenic ★★ same condition
POR p.Arg551Ter Pathogenic/Likely pathogenic ★★ same condition
POR p.Arg613Ter Pathogenic/Likely pathogenic ★★ same condition

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/por-p-val331 (accessed [today's date]).

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