Is PC p.Arg977Trp (c.2929C>T) pathogenic?

PC p.Arg977Trp (c.2929C>T) is classified Uncertain significance in PC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely pathogenic (0.8403); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PC p.Arg977Trp (c.2929C>T)?

PC p.Arg977Trp (c.2929C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PC p.Arg977Trp (c.2929C>T) in the general population?

PC p.Arg977Trp (c.2929C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about PC p.Arg977Trp (c.2929C>T)?

AlphaMissense predicts likely pathogenic (score 0.8403) — an in-silico prediction, not a clinical call.

PC p.Arg977Trp

c.2929C>T · VCV4131567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8403 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8403	likely pathogenic
REVEL	0.881	moderately pathogenic-leaning
SaProt	LLR -16.76	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 23 kb · p 3.1e-25 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,996 alleles

Overall 6.2e-05% 1/1,613,670 alleles · very rare exomes 0/1,461,502 · genomes 1/152,168 · 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: PC
Protein: p.Arg977Trp
Coding: c.2929C>T
MANE Select: NM_001040716
Type: single nucleotide variant
Location: chr11:66849829 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.07 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.53 · 10 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PC p.Arg977Gln Uncertain significance ★ ⚠ same residue
PC p.Ala280Thr Uncertain significance ★★ ⚠ same condition
PC p.Ala431Gly Uncertain significance ★★ ⚠ same condition
PC p.Arg31His Uncertain significance ★★ ⚠ same condition
PC p.Arg385Cys Uncertain significance ★★ ⚠ same condition
PC p.Arg393Cys Uncertain significance ★★ ⚠ same condition
PC p.Arg77Trp Uncertain significance ★★ ⚠ same condition
PC p.Asp1067Asn Uncertain significance ★★ ⚠ same condition

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/pc-p-arg977trp (accessed [today's date]).

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