Is MRPL44 p.Ala331Val (c.992C>T) pathogenic?

MRPL44 p.Ala331Val (c.992C>T) is classified Uncertain significance in MRPL44 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-20). AlphaMissense: likely benign (0.0907); Very rare (popmax 0.000255%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MRPL44 p.Ala331Val (c.992C>T)?

MRPL44 p.Ala331Val (c.992C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MRPL44 p.Ala331Val (c.992C>T) in the general population?

MRPL44 p.Ala331Val (c.992C>T) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about MRPL44 p.Ala331Val (c.992C>T)?

AlphaMissense predicts likely benign (score 0.0907) — an in-silico prediction, not a clinical call.

MRPL44 p.Ala331Val

c.992C>T · rs1312476236 · VCV2406021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0907 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0907	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -6.42	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 1.6	GERP 2.7, phastCons 0.82
Regional constraint	o/e 1.03	unconstrained · MANE · 9,558 bp · p 0.58 · regional, not allelic
Overall
CADD	18.09	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 0.000255% European (non-Finnish) · 3/1,177,012 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000187% 3/1,608,258 alleles · very rare exomes 3/1,455,966 · genomes 0/152,292 · joint denominator

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: MRPL44
Protein: p.Ala331Val
Coding: c.992C>T
MANE Select: NM_022915
dbSNP: rs1312476236
Type: single nucleotide variant
Location: chr2:223967027 (GRCh38)
Gene constraint: LOEUF 1.194 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.36 · 91 PDB

Full MRPL44 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MRPL44 p.Ala331= Likely benign ★ same residue
MRPL44 p.Arg105Cys Uncertain significance ★★ ⚠ same condition
MRPL44 p.Arg312Trp Uncertain significance ★★ ⚠ same condition
MRPL44 p.Asn249Ser Uncertain significance ★★ ⚠ same condition
MRPL44 p.Asn315Tyr Uncertain significance ★★ ⚠ same condition
MRPL44 p.Ile153Leu Uncertain significance ★★ ⚠ same condition
MRPL44 p.Leu137Val Uncertain significance ★★ ⚠ same condition
MRPL44 p.Phe35Val 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/mrpl44-p-ala331val (accessed [today's date]).

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