Is LRRC7 p.Ser392Pro (c.1174T>C) pathogenic?

LRRC7 p.Ser392Pro (c.1174T>C) is classified Uncertain significance in LRRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-07-15). No allele count reported in gnomAD v4.1 (AN 1,585,366); Associated with intellectual developmental disorder, autosomal dominant 77.

What condition is associated with LRRC7 p.Ser392Pro (c.1174T>C)?

LRRC7 p.Ser392Pro (c.1174T>C) is associated with intellectual developmental disorder, autosomal dominant 77 (ClinVar).

How common is LRRC7 p.Ser392Pro (c.1174T>C) in the general population?

LRRC7 p.Ser392Pro (c.1174T>C) is no allele count reported in gnomAD v4.1 (AN 1,585,366) (gnomAD).

LRRC7 p.Ser392Pro

c.1174T>C · VCV4879643

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,585,366)

Conditions

intellectual developmental disorder, autosomal dominant 77

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.301	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 261 kb · p 2.1e-37 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,585,366). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LRRC7
Protein: p.Ser392Pro
Coding: c.1174T>C
MANE Select: NM_001370785
Type: single nucleotide variant
Location: chr1:70013013 (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

Disease context

intellectual developmental disorder, autosomal dominant 77 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LRRC7 p.Leu135His Uncertain significance ★ same condition
LRRC7 p.Ser907Thr Uncertain significance ★ same condition
LRRC7 p.Thr355Ala Uncertain significance ★ same condition
LRRC7 p.Thr903Ile Uncertain significance ★ same condition
LRRC7 p.Tyr1210Ter Uncertain significance ★ same condition
LRRC7 p.Asn94Ser Pathogenic same condition
LRRC7 p.Leu296Pro Pathogenic same condition
LRRC7 c.932-12_932-10del 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/lrrc7-p-ser392pro (accessed [today's date]).

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