Is OPLAH p.Phe488Ser (c.1463T>C) pathogenic?

OPLAH p.Phe488Ser (c.1463T>C) is classified Uncertain significance in OPLAH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-19). AlphaMissense: likely pathogenic (0.9795); Absent from gnomAD v4.1.

How common is OPLAH p.Phe488Ser (c.1463T>C) in the general population?

OPLAH p.Phe488Ser (c.1463T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OPLAH p.Phe488Ser (c.1463T>C)?

AlphaMissense predicts likely pathogenic (score 0.9795) — an in-silico prediction, not a clinical call.

OPLAH p.Phe488Ser

c.1463T>C · VCV3410091

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9795 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9795	likely pathogenic · top 8% in OPLAH
REVEL	0.636	indeterminate
SaProt	LLR -13.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 7,706 bp · p 0.038 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OPLAH
Protein: p.Phe488Ser
Coding: c.1463T>C
MANE Select: NM_017570
Type: single nucleotide variant
Location: chr8:144057280 (GRCh38)
Gene constraint: LOEUF 1.163 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.08

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

Similar variants

OPLAH c.587+1G>A Pathogenic/Likely pathogenic ★★ same type
OPLAH p.Gln1006Ter Pathogenic/Likely pathogenic ★★ same type
OPLAH p.Tyr248Ter Likely pathogenic ★★ same type
OPLAH p.Ala1093Val Uncertain significance ★★ ⚠ same type
OPLAH p.Ala344Thr Uncertain significance ★★ ⚠ same type
OPLAH p.Ala422Val Uncertain significance ★★ ⚠ same type
OPLAH p.Ala46Thr Uncertain significance ★★ ⚠ same type
OPLAH p.Ala475Val 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/oplah-p-phe488ser (accessed [today's date]).

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