Is EDF1 p.Ala147Val (c.440C>T) pathogenic?

EDF1 p.Ala147Val (c.440C>T) is classified Uncertain significance in EDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-05). AlphaMissense: likely benign (0.0978); Very rare (popmax 0.00364%, nfe).

How common is EDF1 p.Ala147Val (c.440C>T) in the general population?

EDF1 p.Ala147Val (c.440C>T) is very rare (popmax 0.00364%, nfe) (gnomAD).

What do computational predictors say about EDF1 p.Ala147Val (c.440C>T)?

AlphaMissense predicts likely benign (score 0.0978) — an in-silico prediction, not a clinical call.

EDF1 p.Ala147Val

c.440C>T · rs746827500 · VCV3087187

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0978 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0978	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -7.71	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 6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,971 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	22.1	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 0.00364% European (non-Finnish) · 43/1,179,986 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00279% 45/1,613,746 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,442
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
South Asian	0.0011%	91,050

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.Ala147Val
Coding: c.440C>T
MANE Select: NM_003792
dbSNP: rs746827500
Type: single nucleotide variant
Location: chr9:136862291 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 83.47 · 7 PDB

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

Similar variants

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
EDF1 p.Ser4Arg 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-ala147val (accessed [today's date]).

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