Is MATR3 p.Phe5= (c.15C>T) pathogenic?

MATR3 p.Phe5= (c.15C>T) is classified Likely benign in MATR3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-27). Ultra-rare (popmax 0.024%, afr); Associated with amyotrophic lateral sclerosis type 21.

What condition is associated with MATR3 p.Phe5= (c.15C>T)?

MATR3 p.Phe5= (c.15C>T) is associated with amyotrophic lateral sclerosis type 21 (ClinVar).

How common is MATR3 p.Phe5= (c.15C>T) in the general population?

MATR3 p.Phe5= (c.15C>T) is ultra-rare (popmax 0.024%, afr) (gnomAD).

MATR3 p.Phe5=

c.15C>T · rs184609870 · VCV351120

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Conditions

amyotrophic lateral sclerosis type 21

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 6	GERP 0.92, phastCons 1
Overall
CADD	13.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% African / African-American · 18/74,936 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00136% 22/1,613,846 alleles · ultra-rare exomes 19/1,461,730 · genomes 3/152,116 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,163
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)	8.48e-05%	1,179,916

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: MATR3
Protein: p.Phe5=
Coding: c.15C>T
MANE Select: NM_018834
dbSNP: rs184609870
Type: single nucleotide variant
Location: chr5:139307430 (GRCh38)
Gene constraint: LOEUF 0.122 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 57.64

Full MATR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

amyotrophic lateral sclerosis type 21 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MATR3 p.Ser85Cys Pathogenic ★★ same condition
MATR3 p.Ala108Ser Uncertain significance ★★ same condition
MATR3 p.Ala745Val Uncertain significance ★★ ⚠ same condition
MATR3 p.Arg102His Uncertain significance ★★ ⚠ same condition
MATR3 p.Arg127Cys Uncertain significance ★★ ⚠ same condition
MATR3 p.Arg167Trp Uncertain significance ★★ ⚠ same condition
MATR3 p.Arg19His Uncertain significance ★★ ⚠ same condition
MATR3 p.Arg317Leu 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/matr3-p-phe5 (accessed [today's date]).

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