Is LRRC7 p.Phe1072= (c.3216C>T) pathogenic?

LRRC7 p.Phe1072= (c.3216C>T) is classified Likely benign in LRRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-01). Rare (popmax 0.16%, amr).

How common is LRRC7 p.Phe1072= (c.3216C>T) in the general population?

LRRC7 p.Phe1072= (c.3216C>T) is rare (popmax 0.16%, amr) (gnomAD).

LRRC7 p.Phe1072=

c.3216C>T · VCV4681797

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.16%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.5, phastCons 1
Overall
CADD	6.508	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.16% Admixed American · 96/59,994 alleles

Filtering AF 0.134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.0062% 100/1,613,946 alleles · rare exomes 94/1,461,788 · genomes 6/152,158 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.16%	625
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00133%	74,920

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.Phe1072=
Coding: c.3216C>T
MANE Select: NM_001370785
Type: single nucleotide variant
Location: chr1:70039040 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.05 · 2 PDB
Residue 1072: a UniProt-annotated variant site (in mrd77; likely pathogenic); a UniProt-annotated variant site (in mrd77; likely pathogenic; loss of interaction with ctnnd2; decreased interaction with camk2a)

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-phe1072 (accessed [today's date]).

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