Is PDSS2 p.Ser127= (c.381C>T) pathogenic?

PDSS2 p.Ser127= (c.381C>T) is classified Likely benign in PDSS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). Very rare (popmax 0.00333%, amr).

How common is PDSS2 p.Ser127= (c.381C>T) in the general population?

PDSS2 p.Ser127= (c.381C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

PDSS2 p.Ser127=

c.381C>T · VCV4697391

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 -3.7	GERP -5.7
Overall
CADD	0.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,008 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00031% 5/1,613,580 alleles · very rare exomes 5/1,461,466 · genomes 0/152,114 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,004
South Asian	0.0011%	91,054
European (non-Finnish)	0.00017%	589,849

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.Ser127=
Coding: c.381C>T
MANE Select: NM_020381
Type: single nucleotide variant
Location: chr6:107334248 (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.Ser127Asn Uncertain significance ★ ⚠ same residue
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

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-ser127 (accessed [today's date]).

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