Is ELF1 p.Pro164Leu (c.491C>T) pathogenic?

ELF1 p.Pro164Leu (c.491C>T) is classified Uncertain significance in ELF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-18). AlphaMissense: likely benign (0.0616); Ultra-rare (popmax 0.015%, amr).

How common is ELF1 p.Pro164Leu (c.491C>T) in the general population?

ELF1 p.Pro164Leu (c.491C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about ELF1 p.Pro164Leu (c.491C>T)?

AlphaMissense predicts likely benign (score 0.0616) — an in-silico prediction, not a clinical call.

ELF1 p.Pro164Leu

c.491C>T · rs138109960 · VCV2462340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0616 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0616	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -7.01	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 5.8	GERP 1.6, phastCons 1
Overall
CADD	21.4	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 0.015% Admixed American · 9/59,982 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.0112% 181/1,613,836 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.318%	315
Remaining individualsnot grpmax-eligible	0.0384%	2,604
Admixed Americangrpmax	0.015%	6,665
East Asian	0.00668%	14,964
African / African-American	0.00534%	18,713
European (non-Finnish)	0.00381%	26,222
South Asian	0.0022%	45,533

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro164Leu
Coding: c.491C>T
MANE Select: NM_032377 · reported on NM_172373
dbSNP: rs138109960
Type: single nucleotide variant
Location: chr13:40949844 (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-pro164leu (accessed [today's date]).

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