Is PGC p.Ser232Asn (c.695G>A) pathogenic?

PGC p.Ser232Asn (c.695G>A) is classified Likely benign in PGC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.0702); Very rare (popmax 0.00168%, amr).

How common is PGC p.Ser232Asn (c.695G>A) in the general population?

PGC p.Ser232Asn (c.695G>A) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about PGC p.Ser232Asn (c.695G>A)?

AlphaMissense predicts likely benign (score 0.0702) — an in-silico prediction, not a clinical call.

PGC p.Ser232Asn

c.695G>A · rs375050676 · VCV3211776

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0702 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0702	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -7.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.44	GERP -0.58
Regional constraint	o/e 0.97	unconstrained · MANE · 10 kb · p 0.46 · regional, not allelic
Overall
CADD	0.061	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% Admixed American · 1/59,450 alleles

Overall 6.22e-05% 1/1,608,710 alleles · very rare exomes 1/1,456,410 · genomes 0/152,300 · joint denominator

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: PGC
Protein: p.Ser232Asn
Coding: c.695G>A
MANE Select: NM_002630
dbSNP: rs375050676
Type: single nucleotide variant
Location: chr6:41740563 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 2 PDB
Residue 232: the peptidase a1 domain; an α-helix

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

Similar variants

PGC p.Ala174Val Uncertain significance ★ ⚠ same type
PGC p.Ala183Thr Uncertain significance ★ ⚠ same type
PGC p.Ala186Val Uncertain significance ★ ⚠ same type
PGC p.Ala224Pro Uncertain significance ★ ⚠ same type
PGC p.Ala242Val Uncertain significance ★ ⚠ same type
PGC p.Ala388Thr Uncertain significance ★ ⚠ same type
PGC p.Ala67Gly Uncertain significance ★ ⚠ same type
PGC p.Ala67Val 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/pgc-p-ser232asn (accessed [today's date]).

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