Is DDX55 p.Phe418Ser (c.1253T>C) pathogenic?

DDX55 p.Phe418Ser (c.1253T>C) is classified Uncertain significance in DDX55 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: likely pathogenic (0.7665); Very rare (popmax 0.00133%, afr).

How common is DDX55 p.Phe418Ser (c.1253T>C) in the general population?

DDX55 p.Phe418Ser (c.1253T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DDX55 p.Phe418Ser (c.1253T>C)?

AlphaMissense predicts likely pathogenic (score 0.7665) — an in-silico prediction, not a clinical call.

DDX55 p.Phe418Ser

c.1253T>C · VCV3500666

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7665 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7665	likely pathogenic
REVEL	0.195	benign-leaning
SaProt	LLR -11.28	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.36 · regional, not allelic
Overall
CADD	26.9	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 0.00133% African / African-American · 1/74,928 alleles

Overall 0.000657% 1/152,180 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: DDX55
Protein: p.Phe418Ser
Coding: c.1253T>C
MANE Select: NM_020936
Type: single nucleotide variant
Location: chr12:123618757 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.56

Full DDX55 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX55 p.Ala153Asp Uncertain significance ★ ⚠ same type
DDX55 p.Ala215Val Uncertain significance ★ ⚠ same type
DDX55 p.Ala235Val Uncertain significance ★ ⚠ same type
DDX55 p.Ala38Thr Uncertain significance ★ ⚠ same type
DDX55 p.Ala401Pro Uncertain significance ★ ⚠ same type
DDX55 p.Ala456Pro Uncertain significance ★ ⚠ same type
DDX55 p.Arg144Cys Uncertain significance ★ ⚠ same type
DDX55 p.Arg218Gln 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/ddx55-p-phe418ser (accessed [today's date]).

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