Is MATN3 p.Pro4Ser (c.10C>T) pathogenic?

MATN3 p.Pro4Ser (c.10C>T) is classified Uncertain significance in MATN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). AlphaMissense: likely benign (0.0888); No allele count reported in gnomAD v4.1 (AN 1,215,632).

How common is MATN3 p.Pro4Ser (c.10C>T) in the general population?

MATN3 p.Pro4Ser (c.10C>T) is no allele count reported in gnomAD v4.1 (AN 1,215,632) (gnomAD).

What do computational predictors say about MATN3 p.Pro4Ser (c.10C>T)?

AlphaMissense predicts likely benign (score 0.0888) — an in-silico prediction, not a clinical call.

MATN3 p.Pro4Ser

c.10C>T · rs2527712944 · VCV2119086

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0888 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,215,632)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0888	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.74	GERP -2.6, phastCons 0.12
Regional constraint	o/e 0.95	unconstrained · MANE · 20 kb · p 0.25 · regional, not allelic
Overall
CADD	14.31	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

No allele count reported in gnomAD v4.1 (AN 1,215,632). 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: MATN3
Protein: p.Pro4Ser
Coding: c.10C>T
MANE Select: NM_002381
dbSNP: rs2527712944
Type: single nucleotide variant
Location: chr2:20012622 (GRCh38)
Gene constraint: LOEUF 1.358 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 79.79

Full MATN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MATN3 p.Ala219Asp Pathogenic/Likely pathogenic ★★ same type
MATN3 p.Arg121Trp Pathogenic/Likely pathogenic ★★ same type
MATN3 p.Thr120Met Pathogenic/Likely pathogenic ★★ same type
MATN3 p.Ala139Gly Uncertain significance ★★ ⚠ same type
MATN3 p.Ala173Asp Uncertain significance ★★ ⚠ same type
MATN3 p.Ala207Val Uncertain significance ★★ ⚠ same type
MATN3 p.Ala56Pro Uncertain significance ★★ ⚠ same type
MATN3 p.Ala62Val 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/matn3-p-pro4ser (accessed [today's date]).

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