Is EDC3 p.Phe54Ser (c.161T>C) pathogenic?

EDC3 p.Phe54Ser (c.161T>C) is classified Pathogenic in EDC3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-12-02). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1; Associated with intellectual disability, autosomal recessive 50.

What condition is associated with EDC3 p.Phe54Ser (c.161T>C)?

EDC3 p.Phe54Ser (c.161T>C) is associated with intellectual disability, autosomal recessive 50 (ClinVar).

How common is EDC3 p.Phe54Ser (c.161T>C) in the general population?

EDC3 p.Phe54Ser (c.161T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDC3 p.Phe54Ser (c.161T>C)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

EDC3 p.Phe54Ser

c.161T>C · rs1057517676 · VCV372218

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal recessive 50

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar · top 1% in EDC3
REVEL	0.798	moderately pathogenic-leaning
SaProt	LLR -14.65	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 19 kb · p 0.0048 · regional, not allelic
Overall
CADD	29.7	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: EDC3
Protein: p.Phe54Ser
Coding: c.161T>C
MANE Select: NM_025083
dbSNP: rs1057517676
Type: single nucleotide variant
Location: chr15:74674964 (GRCh38)
Gene constraint: LOEUF 0.656 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 77.04 · 6 PDB
Residue 54: the sm domain; a UniProt-annotated variant site (in mrt50; does not enhance dcp2 decapping activity); a β-strand; the 'required for p-body targeting and interaction with dcp1a' region

Full EDC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal recessive 50 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EDC3 p.Arg260Trp Uncertain significance ★★ ⚠ same condition
EDC3 p.Gln171fs Pathogenic ★ same condition
EDC3 p.Thr273= Benign ★★ same type
EDC3 c.821-2A>C Uncertain significance ★ same type
EDC3 p.Ala129Thr Uncertain significance ★ ⚠ same type
EDC3 p.Ala172Pro Uncertain significance ★ ⚠ same type
EDC3 p.Ala312Thr Uncertain significance ★ ⚠ same type
EDC3 p.Arg232His 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/edc3-p-phe54ser (accessed [today's date]).

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