Is RPL6 p.Val80Phe (c.238G>T) pathogenic?

RPL6 p.Val80Phe (c.238G>T) is classified Uncertain significance in RPL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: likely benign (0.3348); Very rare (popmax 0.00449%, nfe).

How common is RPL6 p.Val80Phe (c.238G>T) in the general population?

RPL6 p.Val80Phe (c.238G>T) is very rare (popmax 0.00449%, nfe) (gnomAD).

What do computational predictors say about RPL6 p.Val80Phe (c.238G>T)?

AlphaMissense predicts likely benign (score 0.3348) — an in-silico prediction, not a clinical call.

RPL6 p.Val80Phe

c.238G>T · VCV3790419

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3348 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3348	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -9.26	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 -0.74	GERP -3.8, phastCons 0.009
Regional constraint	o/e 0.78	unconstrained · MANE · 3,429 bp · p 2.4e-05 · regional, not allelic
Overall
CADD	18.67	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 0.00449% European (non-Finnish) · 53/1,180,020 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00341% 55/1,614,020 alleles · very rare exomes 53/1,461,844 · genomes 2/152,176 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00449%	22,265
African / African-American	0.00267%	37,453

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: RPL6
Protein: p.Val80Phe
Coding: c.238G>T
MANE Select: NM_000970
Type: single nucleotide variant
Location: chr12:112408338 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.21 · 186 PDB
Residue 80: a turn

Full RPL6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPL6 p.Ala169Val Uncertain significance ★ ⚠ same type
RPL6 p.Arg110His Uncertain significance ★ ⚠ same type
RPL6 p.Arg123Gly Uncertain significance ★ ⚠ same type
RPL6 p.Arg156Cys Uncertain significance ★ ⚠ same type
RPL6 p.Arg158Gly Uncertain significance ★ ⚠ same type
RPL6 p.Arg158Lys Uncertain significance ★ ⚠ same type
RPL6 p.Arg183Gln Uncertain significance ★ ⚠ same type
RPL6 p.Arg223Gln 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/rpl6-p-val80phe (accessed [today's date]).

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