Is ATOSA p.Phe508Leu (c.1524C>G) pathogenic?

ATOSA p.Phe508Leu (c.1524C>G) is classified Uncertain significance in ATOSA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-22). AlphaMissense: ambiguous (0.4162); Very rare (popmax 8.48e-05%, nfe).

How common is ATOSA p.Phe508Leu (c.1524C>G) in the general population?

ATOSA p.Phe508Leu (c.1524C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ATOSA p.Phe508Leu (c.1524C>G)?

AlphaMissense predicts ambiguous (score 0.4162) — an in-silico prediction, not a clinical call.

ATOSA p.Phe508Leu

c.1524C>G · VCV4171470

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4162 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4162	ambiguous
REVEL	0.028	moderately benign-leaning
SaProt	LLR -7.18	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.27, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 17 kb · p 0.027 · regional, not allelic
Overall
CADD	15.22	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 8.48e-05% European (non-Finnish) · 1/1,179,870 alleles

Overall 6.84e-05% 1/1,461,632 alleles · very rare

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: ATOSA
Protein: p.Phe508Leu
Coding: c.1524C>G
MANE Select: NM_001385016
Type: single nucleotide variant
Location: chr15:52609390 (GRCh38)
Structure: AlphaFold pLDDT 55.15

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

Similar variants

ATOSA p.Ala116Val Uncertain significance ★ ⚠ same type
ATOSA p.Ala121Val Uncertain significance ★ ⚠ same type
ATOSA p.Ala294Gly Uncertain significance ★ ⚠ same type
ATOSA p.Ala375Pro Uncertain significance ★ ⚠ same type
ATOSA p.Arg1012Gln Uncertain significance ★ ⚠ same type
ATOSA p.Arg134Gln Uncertain significance ★ ⚠ same type
ATOSA p.Arg266Cys Uncertain significance ★ ⚠ same type
ATOSA p.Arg266His 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/atosa-p-phe508leu (accessed [today's date]).

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