Is LRRC7 p.Ser300Phe (c.899C>T) pathogenic?

LRRC7 p.Ser300Phe (c.899C>T) is classified Uncertain significance in LRRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). Very rare (popmax 0.00133%, afr).

How common is LRRC7 p.Ser300Phe (c.899C>T) in the general population?

LRRC7 p.Ser300Phe (c.899C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

LRRC7 p.Ser300Phe

c.899C>T · rs2523321484 · VCV2339632

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.476	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 261 kb · p 2.1e-37 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,982 alleles

Overall 6.2e-05% 1/1,613,068 alleles · very rare exomes 1/1,460,868 · genomes 0/152,200 · 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: LRRC7
Protein: p.Ser300Phe
Coding: c.899C>T
MANE Select: NM_001370785
dbSNP: rs2523321484
Type: single nucleotide variant
Location: chr1:69986354 (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-ser300phe (accessed [today's date]).

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