Is EDC3 p.Pro86Thr (c.256C>A) pathogenic?

EDC3 p.Pro86Thr (c.256C>A) is classified Likely benign in EDC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-23). AlphaMissense: likely benign (0.057); Rare (popmax 0.173%, amr).

How common is EDC3 p.Pro86Thr (c.256C>A) in the general population?

EDC3 p.Pro86Thr (c.256C>A) is rare (popmax 0.173%, amr) (gnomAD).

What do computational predictors say about EDC3 p.Pro86Thr (c.256C>A)?

AlphaMissense predicts likely benign (score 0.057) — an in-silico prediction, not a clinical call.

EDC3 p.Pro86Thr

c.256C>A · rs147438242 · VCV751757

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.057 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.173%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.057	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -6.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.47	GERP -0.098, phastCons 0.99
Regional constraint	o/e 0.82	unconstrained · MANE · 19 kb · p 0.0048 · regional, not allelic
Overall
CADD	8.315	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 0.173% Admixed American · 104/59,972 alleles

Filtering AF 0.146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.00644% 104/1,613,946 alleles · 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: EDC3
Protein: p.Pro86Thr
Coding: c.256C>A
MANE Select: NM_025083
dbSNP: rs147438242
Type: single nucleotide variant
Location: chr15:74671683 (GRCh38)
Gene constraint: LOEUF 0.656 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 77.04 · 6 PDB

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

Similar variants

EDC3 p.Arg260Trp Uncertain significance ★★ ⚠ same type
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
EDC3 p.Arg243Gln 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-pro86thr (accessed [today's date]).

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