Is MRPS34 p.Ser84Phe (c.251C>T) pathogenic?

MRPS34 p.Ser84Phe (c.251C>T) is classified Uncertain significance in MRPS34 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-18). AlphaMissense: likely pathogenic (0.7448); Very rare (popmax 0.00144%, nfe).

How common is MRPS34 p.Ser84Phe (c.251C>T) in the general population?

MRPS34 p.Ser84Phe (c.251C>T) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about MRPS34 p.Ser84Phe (c.251C>T)?

AlphaMissense predicts likely pathogenic (score 0.7448) — an in-silico prediction, not a clinical call.

MRPS34 p.Ser84Phe

c.251C>T · rs964306396 · VCV2182042

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7448 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.7448	likely pathogenic
REVEL	0.365	indeterminate
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 895 bp · p 4.8e-06 · regional, not allelic
Overall
CADD	31.0	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 0.00144% European (non-Finnish) · 16/1,110,274 alleles

Filtering AF 0.000853% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00069%

Overall 0.00124% 18/1,453,386 alleles · very rare exomes 16/1,301,134 · genomes 2/152,252 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00356%	28,074
European (non-Finnish)grpmax	0.00144%	69,392

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MRPS34
Protein: p.Ser84Phe
Coding: c.251C>T
MANE Select: NM_023936
dbSNP: rs964306396
Type: single nucleotide variant
Location: chr16:1772869 (GRCh38)

Full MRPS34 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/mrps34-p-ser84phe (accessed [today's date]).

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