Is LYRM7 p.Pro100Ser (c.298C>T) pathogenic?

LYRM7 p.Pro100Ser (c.298C>T) is classified Uncertain significance in LYRM7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely benign (0.1913); Very rare (popmax 8.51e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LYRM7 p.Pro100Ser (c.298C>T)?

LYRM7 p.Pro100Ser (c.298C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LYRM7 p.Pro100Ser (c.298C>T) in the general population?

LYRM7 p.Pro100Ser (c.298C>T) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about LYRM7 p.Pro100Ser (c.298C>T)?

AlphaMissense predicts likely benign (score 0.1913) — an in-silico prediction, not a clinical call.

LYRM7 p.Pro100Ser

c.298C>T · VCV4624047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1913 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1913	likely benign
REVEL	0.411	indeterminate
SaProt	LLR -8.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 29 kb · p 0.71 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51e-05% European (non-Finnish) · 1/1,175,228 alleles

Overall 6.23e-05% 1/1,604,090 alleles · very rare exomes 1/1,452,228 · genomes 0/151,862 · 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: LYRM7
Protein: p.Pro100Ser
Coding: c.298C>T
MANE Select: NM_181705
Type: single nucleotide variant
Location: chr5:131199584 (GRCh38)
Gene constraint: LOEUF 1.892 · pLI 0.16 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.70

Full LYRM7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LYRM7 p.Asp61Asn Uncertain significance ★★ ⚠ same condition
LYRM7 p.Gly2Glu Uncertain significance ★★ ⚠ same condition
LYRM7 p.Lys82Asn Uncertain significance ★★ ⚠ same condition
LYRM7 p.Thr17Ala Uncertain significance ★★ ⚠ same condition
LYRM7 p.Ile34Leu Benign/Likely benign ★★ same condition
LYRM7 p.Arg3Leu Uncertain significance ★ ⚠ same condition
LYRM7 p.Thr47Pro Uncertain significance ★ ⚠ same condition
LYRM7 p.Val5Leu 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/lyrm7-p-pro100ser (accessed [today's date]).

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