Is EDRF1 p.Pro60Ser (c.178C>T) pathogenic?

EDRF1 p.Pro60Ser (c.178C>T) is classified Uncertain significance in EDRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-24). AlphaMissense: likely benign (0.2915); Ultra-rare (popmax 0.0334%, eas).

How common is EDRF1 p.Pro60Ser (c.178C>T) in the general population?

EDRF1 p.Pro60Ser (c.178C>T) is ultra-rare (popmax 0.0334%, eas) (gnomAD).

What do computational predictors say about EDRF1 p.Pro60Ser (c.178C>T)?

AlphaMissense predicts likely benign (score 0.2915) — an in-silico prediction, not a clinical call.

EDRF1 p.Pro60Ser

c.178C>T · VCV3274522

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2915 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2915	likely benign
REVEL	0.227	benign-leaning
SaProt	LLR -5.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.3	GERP 0.72, phastCons 0.93
Regional constraint	o/e 0.53	unconstrained · MANE · 4,185 bp · p 1.3e-10 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% East Asian · 15/44,882 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.00109% 16/1,461,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0334%	2,992
European (non-Finnish)	8.47e-05%	1,180,048

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.Pro60Ser
Coding: c.178C>T
MANE Select: NM_001202438
Type: single nucleotide variant
Location: chr10:125721273 (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-pro60ser (accessed [today's date]).

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