Is MRPL19 p.Pro71Ser (c.211C>T) pathogenic?

MRPL19 p.Pro71Ser (c.211C>T) is classified Uncertain significance in MRPL19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-12). AlphaMissense: likely benign (0.0753); Ultra-rare (popmax 0.0994%, mid).

How common is MRPL19 p.Pro71Ser (c.211C>T) in the general population?

MRPL19 p.Pro71Ser (c.211C>T) is ultra-rare (popmax 0.0994%, mid) (gnomAD).

What do computational predictors say about MRPL19 p.Pro71Ser (c.211C>T)?

AlphaMissense predicts likely benign (score 0.0753) — an in-silico prediction, not a clinical call.

MRPL19 p.Pro71Ser

c.211C>T · rs377418255 · VCV2227607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0753 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0994%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0753	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -7.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.16	GERP -4
Regional constraint	o/e 1.04	unconstrained · MANE · 8,474 bp · p 0.39 · regional, not allelic
Overall
CADD	0.211	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 0.0994% Middle Eastern · 6/6,034 alleles

Filtering AF 0.0433% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.00759% 120/1,580,522 alleles · ultra-rare exomes 111/1,428,302 · genomes 9/152,220 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0994%	1,006
European (non-Finnish)	0.00911%	10,972
Remaining individualsnot grpmax-eligible	0.00654%	15,297
South Asian	0.00232%	43,065
Admixed American	0.0018%	55,614
African / African-American	0.00135%	74,264

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: MRPL19
Protein: p.Pro71Ser
Coding: c.211C>T
MANE Select: NM_014763
dbSNP: rs377418255
Type: single nucleotide variant
Location: chr2:75647209 (GRCh38)
Gene constraint: LOEUF 1.373 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.98 · 93 PDB

Full MRPL19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MRPL19 c.658-9C>A Likely benign ★★ same type
MRPL19 p.Ala288Val Uncertain significance ★ ⚠ same type
MRPL19 p.Arg118His Uncertain significance ★ ⚠ same type
MRPL19 p.Arg182Trp Uncertain significance ★ ⚠ same type
MRPL19 p.Arg232Cys Uncertain significance ★ ⚠ same type
MRPL19 p.Arg232His Uncertain significance ★ ⚠ same type
MRPL19 p.Arg235His Uncertain significance ★ ⚠ same type
MRPL19 p.Arg271Lys 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/mrpl19-p-pro71ser (accessed [today's date]).

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