Is ELF1 p.Ile471Phe (c.1411A>T) pathogenic?

ELF1 p.Ile471Phe (c.1411A>T) is classified Uncertain significance in ELF1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-05). AlphaMissense: likely benign (0.1624); Ultra-rare (popmax 0.0223%, nfe).

How common is ELF1 p.Ile471Phe (c.1411A>T) in the general population?

ELF1 p.Ile471Phe (c.1411A>T) is ultra-rare (popmax 0.0223%, nfe) (gnomAD).

What do computational predictors say about ELF1 p.Ile471Phe (c.1411A>T)?

AlphaMissense predicts likely benign (score 0.1624) — an in-silico prediction, not a clinical call.

ELF1 p.Ile471Phe

c.1411A>T · VCV4248173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1624 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1624	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -8.85	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 6.2	GERP 1.5, phastCons 1
Overall
CADD	24.3	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 0.0223% European (non-Finnish) · 263/1,180,048 alleles

Filtering AF 0.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0192%

Overall 0.0168% 271/1,614,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0223%	4,487
African / African-American	0.00801%	12,489
Remaining individualsnot grpmax-eligible	0.0032%	31,245

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: ELF1
Protein: p.Ile471Phe
Coding: c.1411A>T
MANE Select: NM_032377 · reported on NM_172373
Type: single nucleotide variant
Location: chr13:40933874 (GRCh38)
Structure: AlphaFold pLDDT 85.98 · 7 PDB

Full ELF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELF1 p.Leu614= Benign ★★ same type
ELF1 p.Pro364= Benign ★★ same type
ELF1 p.Ala29Thr Uncertain significance ★ ⚠ same type
ELF1 p.Ala353Ser Uncertain significance ★ ⚠ same type
ELF1 p.Ala459Val Uncertain significance ★ ⚠ same type
ELF1 p.Arg323Thr Uncertain significance ★ ⚠ same type
ELF1 p.Arg328Gln Uncertain significance ★ ⚠ same type
ELF1 p.Arg330Lys 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/elf1-p-ile471phe (accessed [today's date]).

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