Is PAM p.Ser113Pro (c.337T>C) pathogenic?

PAM p.Ser113Pro (c.337T>C) is classified Uncertain significance in PAM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: ambiguous (0.4525); Rare (popmax 0.199%, eas).

How common is PAM p.Ser113Pro (c.337T>C) in the general population?

PAM p.Ser113Pro (c.337T>C) is rare (popmax 0.199%, eas) (gnomAD).

What do computational predictors say about PAM p.Ser113Pro (c.337T>C)?

AlphaMissense predicts ambiguous (score 0.4525) — an in-silico prediction, not a clinical call.

PAM p.Ser113Pro

c.337T>C · rs768454476 · VCV2462061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4525 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.199%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4525	ambiguous
REVEL	0.142	moderately benign-leaning
SaProt	LLR -9.96	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -2, phastCons 1
Overall
CADD	19.85	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 0.199% East Asian · 89/44,732 alleles

Filtering AF 0.166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.153%

Overall 0.00561% 89/1,587,478 alleles · rare

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: PAM
Protein: p.Ser113Pro
Coding: c.337T>C
MANE Select: NM_001177306
dbSNP: rs768454476
Type: single nucleotide variant
Location: chr5:102914002 (GRCh38)
Residue 113: the 'disordered' region

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

Similar variants

MYCBP2 p.Asp4042Val Uncertain significance ★★ same type
MYCBP2 p.Asp4087Asn Uncertain significance ★★ same type
MYCBP2 p.Gly877Ala Uncertain significance ★★ ⚠ same type
MYCBP2 p.His2087Leu Uncertain significance ★★ ⚠ same type
MYCBP2 p.Leu3349Phe Uncertain significance ★★ ⚠ same type
MYCBP2 p.Lys2309Ter Uncertain significance ★★ same type
MYCBP2 p.Phe1319Leu Uncertain significance ★★ same type
MYCBP2 p.Tyr962Cys 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/pam-p-ser113pro (accessed [today's date]).

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