Is PDSS2 p.Ile119= (c.357C>T) pathogenic?

PDSS2 p.Ile119= (c.357C>T) is classified Likely benign in PDSS2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-17). Very rare (popmax 0.00534%, afr).

How common is PDSS2 p.Ile119= (c.357C>T) in the general population?

PDSS2 p.Ile119= (c.357C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

PDSS2 p.Ile119=

c.357C>T · rs746405005 · VCV1648008

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

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 1.5	GERP -4.8, phastCons 1
Overall
CADD	6.752	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,852 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000434% 7/1,613,102 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,713
Admixed American	0.00167%	59,980
Remaining individualsnot grpmax-eligible	0.0016%	62,456
European (non-Finnish)	8.48e-05%	1,179,338

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: PDSS2
Protein: p.Ile119=
Coding: c.357C>T
MANE Select: NM_020381
dbSNP: rs746405005
Type: single nucleotide variant
Location: chr6:107334272 (GRCh38)
Gene constraint: LOEUF 0.818 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.28

Full PDSS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDSS2 p.Arg163His Uncertain significance ★★ ⚠ same type
PDSS2 p.Arg366Cys Uncertain significance ★★ ⚠ same type
PDSS2 p.Arg366His Uncertain significance ★★ ⚠ same type
PDSS2 p.Arg385Thr Uncertain significance ★★ ⚠ same type
PDSS2 p.Asn167Ser Uncertain significance ★★ ⚠ same type
PDSS2 p.Asn201Ser Uncertain significance ★★ ⚠ same type
PDSS2 p.Asn314Thr Uncertain significance ★★ ⚠ same type
PDSS2 p.Asn390Ser 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/pdss2-p-ile119 (accessed [today's date]).

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