Is LRPPRC p.Ala3Pro (c.7G>C) pathogenic?

LRPPRC p.Ala3Pro (c.7G>C) is classified Uncertain significance in LRPPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-08). AlphaMissense: ambiguous (0.5565); Very rare (popmax 0.00596%, amr).

How common is LRPPRC p.Ala3Pro (c.7G>C) in the general population?

LRPPRC p.Ala3Pro (c.7G>C) is very rare (popmax 0.00596%, amr) (gnomAD).

What do computational predictors say about LRPPRC p.Ala3Pro (c.7G>C)?

AlphaMissense predicts ambiguous (score 0.5565) — an in-silico prediction, not a clinical call.

LRPPRC p.Ala3Pro

c.7G>C · VCV3368894

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5565 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00596%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5565	ambiguous
REVEL	0.191	benign-leaning
SaProt	LLR -9.27	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.83	GERP -0.73, phastCons 0.65
Regional constraint	o/e 1.21	unconstrained · MANE · 107 kb · p 2.9e-18 · regional, not allelic
Overall
CADD	18.35	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 0.00596% Admixed American · 3/50,316 alleles

Filtering AF 0.00158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.001%

Overall 0.00177% 27/1,526,028 alleles · very rare exomes 25/1,373,848 · genomes 2/152,180 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00596%	16,772
Remaining individualsnot grpmax-eligible	0.00336%	29,752
Finnishnot grpmax-eligible	0.00225%	44,486
European (non-Finnish)	0.00184%	54,438

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: LRPPRC
Protein: p.Ala3Pro
Coding: c.7G>C
MANE Select: NM_133259
Type: single nucleotide variant
Location: chr2:43995941 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.35 · 2 PDB

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

Similar variants

LRPPRC p.Ala3Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
LRPPRC p.Ala3Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
LRPPRC p.Ala3Val Uncertain significance ★ ⚠ same residue
LRPPRC p.Ala3= Likely benign ★ same residue
LRPPRC c.1369+1G>C Likely pathogenic ★★ same type
LRPPRC c.1582+7A>G Likely pathogenic ★★ same type
LRPPRC c.1677+1G>A Likely pathogenic ★★ same type
LRPPRC c.1677+1G>T Likely pathogenic ★★ 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/lrpprc-p-ala3pro (accessed [today's date]).

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