Is MRPL38 p.Pro362Ser (c.1084C>T) pathogenic?

MRPL38 p.Pro362Ser (c.1084C>T) is classified Uncertain significance in MRPL38 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). AlphaMissense: ambiguous (0.4461); Ultra-rare (popmax 0.0134%, eas).

How common is MRPL38 p.Pro362Ser (c.1084C>T) in the general population?

MRPL38 p.Pro362Ser (c.1084C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about MRPL38 p.Pro362Ser (c.1084C>T)?

AlphaMissense predicts ambiguous (score 0.4461) — an in-silico prediction, not a clinical call.

MRPL38 p.Pro362Ser

c.1084C>T · rs753569263 · VCV3207668

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4461 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Computational evidence

Protein change
AlphaMissense	0.4461	ambiguous
REVEL	0.441	indeterminate
SaProt	LLR -9.60	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 6,022 bp · p 0.71 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,780 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00395%

Overall 0.000434% 7/1,611,138 alleles · ultra-rare exomes 6/1,459,112 · genomes 1/152,026 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,463
European (non-Finnish)	8.48e-05%	1,179,268

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: MRPL38
Protein: p.Pro362Ser
Coding: c.1084C>T
MANE Select: NM_032478
dbSNP: rs753569263
Type: single nucleotide variant
Location: chr17:75898909 (GRCh38)
Gene constraint: LOEUF 1.308 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.80 · 92 PDB

Full MRPL38 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MRPL38 p.Ala109Ser Uncertain significance ★ ⚠ same type
MRPL38 p.Ala123Thr Uncertain significance ★ ⚠ same type
MRPL38 p.Arg106Gln Uncertain significance ★ ⚠ same type
MRPL38 p.Arg106Trp Uncertain significance ★ ⚠ same type
MRPL38 p.Arg124His Uncertain significance ★ ⚠ same type
MRPL38 p.Arg136Trp Uncertain significance ★ ⚠ same type
MRPL38 p.Arg170Gln Uncertain significance ★ ⚠ same type
MRPL38 p.Arg244Trp 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/mrpl38-p-pro362ser (accessed [today's date]).

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