Is PRCC p.Ser348Phe (c.1043C>T) pathogenic?

PRCC p.Ser348Phe (c.1043C>T) is classified Uncertain significance in PRCC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-30). AlphaMissense: likely benign (0.2338); Very rare (popmax 0.00334%, amr); Associated with Papillary renal cell carcinoma type 1.

What condition is associated with PRCC p.Ser348Phe (c.1043C>T)?

PRCC p.Ser348Phe (c.1043C>T) is associated with Papillary renal cell carcinoma type 1 (ClinVar).

How common is PRCC p.Ser348Phe (c.1043C>T) in the general population?

PRCC p.Ser348Phe (c.1043C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about PRCC p.Ser348Phe (c.1043C>T)?

AlphaMissense predicts likely benign (score 0.2338) — an in-silico prediction, not a clinical call.

PRCC p.Ser348Phe

c.1043C>T · VCV3892173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2338 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Papillary renal cell carcinoma type 1

Computational evidence

Protein change
AlphaMissense	0.2338	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -10.62	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 4,824 bp · p 0.34 · regional, not allelic
Overall
CADD	26.4	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 0.00334% Admixed American · 2/59,920 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000434% 7/1,611,674 alleles · very rare exomes 5/1,459,500 · genomes 2/152,174 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,960
Remaining individualsnot grpmax-eligible	0.0016%	62,386
European (non-Finnish)	0.00034%	294,533

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: PRCC
Protein: p.Ser348Phe
Coding: c.1043C>T
MANE Select: NM_005973
Type: single nucleotide variant
Location: chr1:156787134 (GRCh38)
Gene constraint: LOEUF 0.403 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.89

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

Disease context

Papillary renal cell carcinoma type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRCC p.Asp341Gly Uncertain significance ★★ ⚠ same condition
PRCC p.Ser241Leu Uncertain significance ★ ⚠ same condition
PRCC p.Ala283Thr Uncertain significance ★ ⚠ same type
PRCC p.Ala356Thr Uncertain significance ★ ⚠ same type
PRCC p.Arg219Thr Uncertain significance ★ ⚠ same type
PRCC p.Arg467Gln Uncertain significance ★ ⚠ same type
PRCC p.Arg482Cys Uncertain significance ★ ⚠ same type
PRCC p.Asn189Ser 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/prcc-p-ser348phe (accessed [today's date]).

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