Is LRMDA p.Arg222Ter (c.664C>T) pathogenic?

LRMDA p.Arg222Ter (c.664C>T) is classified Likely pathogenic in LRMDA (ClinVar, Single submitter, 4 submitters; last evaluated 2025-02-17). Ultra-rare (popmax 0.016%, afr); Associated with oculocutaneous albinism type 7.

What condition is associated with LRMDA p.Arg222Ter (c.664C>T)?

LRMDA p.Arg222Ter (c.664C>T) is associated with oculocutaneous albinism type 7 (ClinVar).

How common is LRMDA p.Arg222Ter (c.664C>T) in the general population?

LRMDA p.Arg222Ter (c.664C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

How is Oculocutaneous albinism type 7 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

LRMDA p.Arg222Ter

c.664C>T · rs587776952 · VCV41916

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Conditions

oculocutaneous albinism type 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.7, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,900 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00217% 35/1,613,710 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,242
East Asian	0.00446%	22,442
European (non-Finnish)	0.0017%	58,988
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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: LRMDA
Protein: p.Arg222Ter
Coding: c.664C>T
MANE Select: NM_001305581
dbSNP: rs587776952
Type: single nucleotide variant
Location: chr10:76557271 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.40

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

Disease context

oculocutaneous albinism type 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Oculocutaneous albinism type 7 (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

LRMDA p.Arg222Gln Uncertain significance ★ ⚠ same residue
LRMDA c.398+31A>C Benign ★★ same condition
LRMDA c.516+53C>T Benign ★★ same condition
LRMDA p.Leu122= Benign ★★ same condition
LRMDA p.Met1Thr Uncertain significance ★ same condition
LRMDA p.Arg184Cys Uncertain significance ★★ ⚠ same type
LRMDA p.Arg207His Uncertain significance ★★ ⚠ same type
LRMDA p.Met166Thr 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/lrmda-p-arg222ter (accessed [today's date]).

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