Is LARP7 p.Arg577Ser (c.1731A>T) pathogenic?

LARP7 p.Arg577Ser (c.1731A>T) is classified Conflicting classifications of pathogenicity in LARP7 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-11-27). AlphaMissense: likely pathogenic (0.7432); Ultra-rare (popmax 0.0851%, sas); Associated with Inborn genetic diseases.

What condition is associated with LARP7 p.Arg577Ser (c.1731A>T)?

LARP7 p.Arg577Ser (c.1731A>T) is associated with Inborn genetic diseases (ClinVar).

How common is LARP7 p.Arg577Ser (c.1731A>T) in the general population?

LARP7 p.Arg577Ser (c.1731A>T) is ultra-rare (popmax 0.0851%, sas) (gnomAD).

What do computational predictors say about LARP7 p.Arg577Ser (c.1731A>T)?

AlphaMissense predicts likely pathogenic (score 0.7432) — an in-silico prediction, not a clinical call.

LARP7 p.Arg577Ser

c.1731A>T · rs374867509 · VCV2168468

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7432 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0851%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7432	likely pathogenic
REVEL	0.263	benign-leaning
SaProt	LLR -6.83	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -3.5, phastCons 0.002
Regional constraint	o/e 1.09	unconstrained · MANE · 13 kb · p 0.021 · regional, not allelic
Overall
CADD	21.2	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 0.0851% South Asian · 73/85,798 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0635%

Overall 0.00588% 93/1,580,372 alleles · ultra-rare exomes 86/1,428,712 · genomes 7/151,660 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0851%	1,175
Remaining individualsnot grpmax-eligible	0.0049%	20,397
African / African-American	0.00271%	36,897
European (non-Finnish)	0.00129%	77,298

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: LARP7
Protein: p.Arg577Ser
Coding: c.1731A>T
MANE Select: NM_016648
dbSNP: rs374867509
Type: single nucleotide variant
Location: chr4:112657309 (GRCh38)
Gene constraint: LOEUF 1.129 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.89 · 5 PDB
Residue 577: a UniProt-annotated variant site (in alazs; reduced 2'-o-methylation of u6 snrnas and defects in mrna splicing)

Full LARP7 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

LARP7 p.Arg577Ile Uncertain significance ★ ⚠ same residue
LARP7 p.Ala324Thr Uncertain significance ★★ ⚠ same condition
LARP7 p.Ala36Thr Uncertain significance ★★ ⚠ same condition
LARP7 p.Arg279Trp Uncertain significance ★★ ⚠ same condition
LARP7 p.Arg291Gly Uncertain significance ★★ ⚠ same condition
LARP7 p.Asn424Ser Uncertain significance ★★ ⚠ same condition
LARP7 p.Asp490Asn Uncertain significance ★★ same condition
LARP7 p.Asp86Asn 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/larp7-p-arg577ser (accessed [today's date]).

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