Is EDRF1 p.Arg1052Trp (c.3154C>T) pathogenic?

EDRF1 p.Arg1052Trp (c.3154C>T) is classified Uncertain significance in EDRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). AlphaMissense: likely pathogenic (0.658); Very rare (popmax 0.00534%, afr).

How common is EDRF1 p.Arg1052Trp (c.3154C>T) in the general population?

EDRF1 p.Arg1052Trp (c.3154C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about EDRF1 p.Arg1052Trp (c.3154C>T)?

AlphaMissense predicts likely pathogenic (score 0.658) — an in-silico prediction, not a clinical call.

EDRF1 p.Arg1052Trp

c.3154C>T · VCV4016264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.658 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.658	likely pathogenic
REVEL	0.175	moderately benign-leaning
SaProt	LLR -6.09	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 4.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 38 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	28.8	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 0.00534% African / African-American · 4/74,894 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000744% 12/1,613,970 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,724
East Asian	0.00223%	44,888
South Asian	0.0011%	91,074
European (non-Finnish)	0.000508%	196,670

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: EDRF1
Protein: p.Arg1052Trp
Coding: c.3154C>T
MANE Select: NM_001202438
Type: single nucleotide variant
Location: chr10:125749442 (GRCh38)
Gene constraint: LOEUF 0.53 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 76.41

Full EDRF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EDRF1 p.Leu159= Benign ★★ same type
EDRF1 p.Thr480= Benign ★★ same type
EDRF1 p.Thr731= Benign ★★ same type
EDRF1 p.Ala1137Ser Uncertain significance ★ ⚠ same type
EDRF1 p.Ala1210Thr Uncertain significance ★ ⚠ same type
EDRF1 p.Ala1228Thr Uncertain significance ★ ⚠ same type
EDRF1 p.Ala203Thr Uncertain significance ★ ⚠ same type
EDRF1 p.Ala226Ser 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/edrf1-p-arg1052trp (accessed [today's date]).

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