Is LRRC7 p.Phe172Ser (c.515T>C) pathogenic?

LRRC7 p.Phe172Ser (c.515T>C) is classified Uncertain significance in LRRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-13). Absent from gnomAD v4.1.

How common is LRRC7 p.Phe172Ser (c.515T>C) in the general population?

LRRC7 p.Phe172Ser (c.515T>C) is absent from gnomAD v4.1 (gnomAD).

LRRC7 p.Phe172Ser

c.515T>C · rs2524226242 · VCV2283762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.729	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 261 kb · p 2.1e-37 · regional, not allelic
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LRRC7
Protein: p.Phe172Ser
Coding: c.515T>C
MANE Select: NM_001370785
dbSNP: rs2524226242
Type: single nucleotide variant
Location: chr1:69834794 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.05 · 2 PDB

Full LRRC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LRRC7 p.Ala1105Thr Uncertain significance ★★ same type
LRRC7 p.Ser354Ala Uncertain significance ★★ same type
LRRC7 p.Arg417= Likely benign ★★ same type
LRRC7 c.787-1G>T Pathogenic ★ same type
LRRC7 p.Gln748Ter Pathogenic ★ same type
LRRC7 p.Gly1049Ter Pathogenic ★ same type
LRRC7 p.Leu122Arg Likely pathogenic ★ same type
LRRC7 c.1005-7T>A 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/lrrc7-p-phe172ser (accessed [today's date]).

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