Is CYP4F22 p.Ser231= (c.693C>T) pathogenic?

CYP4F22 p.Ser231= (c.693C>T) is classified Benign/Likely benign in CYP4F22 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.57%, afr); Associated with autosomal recessive congenital ichthyosis 5.

What condition is associated with CYP4F22 p.Ser231= (c.693C>T)?

CYP4F22 p.Ser231= (c.693C>T) is associated with autosomal recessive congenital ichthyosis 5 (ClinVar).

How common is CYP4F22 p.Ser231= (c.693C>T) in the general population?

CYP4F22 p.Ser231= (c.693C>T) is low-frequency (popmax 1.57%, afr) (gnomAD).

How is Lamellar ichthyosis inherited?

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

CYP4F22 p.Ser231=

c.693C>T · rs149616338 · VCV328435

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.57%, afr)

Conditions

autosomal recessive congenital ichthyosis 5

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 -14
Overall
CADD	0.819	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.57% African / African-American · 1,175/75,040 alleles

Filtering AF 1.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.46%

Overall 0.0955% 1,542/1,614,172 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.57%	64
Admixed American	0.128%	779
Remaining individualsnot grpmax-eligible	0.123%	812
Middle Eastern	0.0495%	2,021
European (non-Finnish)	0.0173%	5,784
East Asian	0.00668%	14,963
South Asian	0.00329%	30,359

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: CYP4F22
Protein: p.Ser231=
Coding: c.693C>T
MANE Select: NM_173483
dbSNP: rs149616338
Type: single nucleotide variant
Location: chr19:15540471 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.59

Full CYP4F22 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive congenital ichthyosis 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Lamellar ichthyosis (Orphanet):

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

Similar variants

CYP4F22 c.940-1G>A Likely pathogenic ★★ same condition
CYP4F22 p.Arg156Cys Pathogenic ★★ same condition
CYP4F22 p.Arg243Cys Pathogenic/Likely pathogenic ★★ same condition
CYP4F22 p.Arg243His Pathogenic ★★ same condition
CYP4F22 p.Arg326Ter Pathogenic ★★ same condition
CYP4F22 p.Arg362Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
CYP4F22 p.Arg362Ter Pathogenic ★★ same condition
CYP4F22 p.Arg372Trp 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/cyp4f22-p-ser231 (accessed [today's date]).

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