Is ELF4 p.Pro660Ala (c.1978C>G) pathogenic?

ELF4 p.Pro660Ala (c.1978C>G) is classified Uncertain significance in ELF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.0836); Absent from gnomAD v4.1.

How common is ELF4 p.Pro660Ala (c.1978C>G) in the general population?

ELF4 p.Pro660Ala (c.1978C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELF4 p.Pro660Ala (c.1978C>G)?

AlphaMissense predicts likely benign (score 0.0836) — an in-silico prediction, not a clinical call.

ELF4 p.Pro660Ala

c.1978C>G · rs2523013938 · VCV2557677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0836 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0836	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -5.13	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 8.8	GERP 0.34, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 2,786 bp · p 0.57 · regional, not allelic
Overall
CADD	20.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ELF4
Protein: p.Pro660Ala
Coding: c.1978C>G
MANE Select: NM_001421
dbSNP: rs2523013938
Type: single nucleotide variant
Location: chrX:130066735 (GRCh38)
Structure: AlphaFold pLDDT 49.77
Residue 660: the 'disordered' region

Full ELF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELF4 p.Gly206Asp Uncertain significance ★★ ⚠ same type
ELF4 p.Ser413Leu Uncertain significance ★★ ⚠ same type
ELF4 p.Ala147Val Benign/Likely benign ★★ same type
ELF4 p.Arg604Cys Benign ★★ same type
ELF4 p.Ser369= Benign ★★ same type
ELF4 p.Thr503= Benign ★★ same type
ELF4 p.Arg185Ter Likely pathogenic ★ same type
ELF4 p.Arg234Ter Pathogenic ★ 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/elf4-p-pro660ala (accessed [today's date]).

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