Is PDSS2 p.Met1Val (c.1A>G) pathogenic?

PDSS2 p.Met1Val (c.1A>G) is classified Uncertain significance in PDSS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-22). Very rare (popmax 0.0011%, sas).

How common is PDSS2 p.Met1Val (c.1A>G) in the general population?

PDSS2 p.Met1Val (c.1A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

PDSS2 p.Met1Val

c.1A>G · rs767963170 · VCV2052737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.353	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,080 alleles

Overall 0.000124% 2/1,613,872 alleles · very rare exomes 2/1,461,614 · genomes 0/152,258 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,080
European (non-Finnish)	8.47e-05%	1,179,979

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.Met1Val
Coding: c.1A>G
MANE Select: NM_020381
dbSNP: rs767963170
Type: single nucleotide variant
Location: chr6:107459285 (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-met1val (accessed [today's date]).

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