Is EDF1 p.Ser4Arg (c.12C>A) pathogenic?

EDF1 p.Ser4Arg (c.12C>A) is classified Uncertain significance in EDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely pathogenic (0.9583); Very rare (popmax 0.00552%, afr).

How common is EDF1 p.Ser4Arg (c.12C>A) in the general population?

EDF1 p.Ser4Arg (c.12C>A) is very rare (popmax 0.00552%, afr) (gnomAD).

What do computational predictors say about EDF1 p.Ser4Arg (c.12C>A)?

AlphaMissense predicts likely pathogenic (score 0.9583) — an in-silico prediction, not a clinical call.

EDF1 p.Ser4Arg

c.12C>A · rs373291770 · VCV2247674

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9583 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00552%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9583	likely pathogenic
REVEL	0.231	benign-leaning
SaProt	LLR -7.97	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 2.4	GERP -1.3, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,971 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	24.2	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 0.00552% African / African-American · 4/72,500 alleles

Filtering AF 0.00179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00107%

Overall 0.000438% 7/1,598,882 alleles · very rare exomes 6/1,446,704 · genomes 1/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00552%	18,125
Remaining individualsnot grpmax-eligible	0.00323%	30,982
South Asian	0.00112%	89,166

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: EDF1
Protein: p.Ser4Arg
Coding: c.12C>A
MANE Select: NM_003792
dbSNP: rs373291770
Type: single nucleotide variant
Location: chr9:136866247 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 83.47 · 7 PDB
Residue 4: a modified residue (phosphoserine)

Full EDF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EDF1 p.Ala147Val Uncertain significance ★ ⚠ same type
EDF1 p.Arg126Trp Uncertain significance ★ ⚠ same type
EDF1 p.Arg133Gln Uncertain significance ★ ⚠ same type
EDF1 p.Asp5Gly Uncertain significance ★ ⚠ same type
EDF1 p.Gln92Arg Uncertain significance ★ ⚠ same type
EDF1 p.Ile137Val Uncertain significance ★ ⚠ same type
EDF1 p.Lys135Glu Uncertain significance ★ ⚠ same type
EDF1 p.Lys15Gln 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/edf1-p-ser4arg (accessed [today's date]).

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