Is TRAF7 p.Ser558Phe (c.1673C>T) pathogenic?

TRAF7 p.Ser558Phe (c.1673C>T) is classified Pathogenic in TRAF7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-02-06). AlphaMissense: likely pathogenic (0.9708); Absent from gnomAD v4.1; Associated with cardiac, facial, and digital anomalies with developmental delay.

What condition is associated with TRAF7 p.Ser558Phe (c.1673C>T)?

TRAF7 p.Ser558Phe (c.1673C>T) is associated with cardiac, facial, and digital anomalies with developmental delay (ClinVar).

How common is TRAF7 p.Ser558Phe (c.1673C>T) in the general population?

TRAF7 p.Ser558Phe (c.1673C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAF7 p.Ser558Phe (c.1673C>T)?

AlphaMissense predicts likely pathogenic (score 0.9708) — an in-silico prediction, not a clinical call.

TRAF7 p.Ser558Phe

c.1673C>T · rs2141297268 · VCV1203798

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9708 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cardiac, facial, and digital anomalies with developmental delay

Computational evidence

Protein change
AlphaMissense	0.9708	likely pathogenic ✓ concordant with ClinVar
REVEL	0.23	benign-leaning
SaProt	LLR -8.89	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 1,993 bp · p 1.7e-10 · regional, not allelic
Overall
CADD	30.0	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

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: TRAF7
Protein: p.Ser558Phe
Coding: c.1673C>T
MANE Select: NM_032271
dbSNP: rs2141297268
Type: single nucleotide variant
Location: chr16:2175880 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.16 · 1 PDB

Full TRAF7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardiac, facial, and digital anomalies with developmental delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRAF7 p.Arg524Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
TRAF7 p.Arg655Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
TRAF7 p.Leu402Val Pathogenic ★★ ⚠ same condition
TRAF7 p.Ser629Asn Pathogenic/Likely pathogenic ★★ ⚠ same condition
TRAF7 p.Arg371Trp Uncertain significance ★★ ⚠ same condition
TRAF7 p.Val554Ile Uncertain significance ★★ ⚠ same condition
TRAF7 p.Arg653Leu Likely pathogenic ★ ⚠ same condition
TRAF7 p.Glu436Lys Likely pathogenic ★ ⚠ same condition

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/traf7-p-ser558phe (accessed [today's date]).

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