Is ADK p.Phe355Val (c.1063T>G) pathogenic?

ADK p.Phe355Val (c.1063T>G) is classified Uncertain significance in ADK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: ambiguous (0.4953); Very rare (popmax 0.00167%, amr).

How common is ADK p.Phe355Val (c.1063T>G) in the general population?

ADK p.Phe355Val (c.1063T>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ADK p.Phe355Val (c.1063T>G)?

AlphaMissense predicts ambiguous (score 0.4953) — an in-silico prediction, not a clinical call.

ADK p.Phe355Val

c.1063T>G · rs2548202833 · VCV2986507

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4953 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.4953	ambiguous
REVEL	0.632	indeterminate
SaProt	LLR -12.84	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 557 kb · p 4.5e-07 · regional, not allelic
Overall
CADD	24.5	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 0.00167% Admixed American · 1/59,980 alleles

Overall 6.2e-05% 1/1,612,260 alleles · very rare exomes 1/1,460,004 · genomes 0/152,256 · 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: ADK
Protein: p.Phe355Val
Coding: c.1063T>G
MANE Select: NM_006721
dbSNP: rs2548202833
Type: single nucleotide variant
Location: chr10:74708419 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.40 · 7 PDB
Residue 355: a UniProt-annotated variant site (in hmakd)

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

Similar variants

ADK p.Ala344Val Pathogenic/Likely pathogenic ★★ same type
ADK p.Arg338Cys Uncertain significance ★★ ⚠ same type
ADK p.Arg338His Uncertain significance ★★ ⚠ same type
ADK p.Asn53Asp Uncertain significance ★★ ⚠ same type
ADK p.Asp305Glu Uncertain significance ★★ ⚠ same type
ADK p.Gln306Leu Uncertain significance ★★ ⚠ same type
ADK p.Ile87Val Uncertain significance ★★ ⚠ same type
ADK p.Lys264Asn 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/adk-p-phe355val (accessed [today's date]).

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