Is ELF2 p.Arg178Cys (c.532C>T) pathogenic?

ELF2 p.Arg178Cys (c.532C>T) is classified Uncertain significance in ELF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely pathogenic (0.7669); Very rare (popmax 0.00216%, nfe).

How common is ELF2 p.Arg178Cys (c.532C>T) in the general population?

ELF2 p.Arg178Cys (c.532C>T) is very rare (popmax 0.00216%, nfe) (gnomAD).

What do computational predictors say about ELF2 p.Arg178Cys (c.532C>T)?

AlphaMissense predicts likely pathogenic (score 0.7669) — an in-silico prediction, not a clinical call.

ELF2 p.Arg178Cys

c.532C>T · VCV4248186

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7669 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00216%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7669	likely pathogenic
REVEL	0.088	moderately benign-leaning
SaProt	LLR -12.80	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 76 kb · p 0.0062 · regional, not allelic
Overall
CADD	33.0	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 0.00216% European (non-Finnish) · 25/1,156,810 alleles

Filtering AF 0.00148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00125%

Overall 0.00165% 26/1,577,508 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00216%	46,272
South Asian	0.00117%	85,676

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: ELF2
Protein: p.Arg178Cys
Coding: c.532C>T
MANE Select: NM_001331036
Type: single nucleotide variant
Location: chr4:139067765 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.58 · 1 PDB
Residue 178: the 'disordered' region

Full ELF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELF2 p.Ala4Thr Likely pathogenic ★ ⚠ same type
ELF2 p.Ala135Pro Uncertain significance ★ ⚠ same type
ELF2 p.Ala368Val Uncertain significance ★ ⚠ same type
ELF2 p.Ala383Val Uncertain significance ★ ⚠ same type
ELF2 p.Ala428Val Uncertain significance ★ ⚠ same type
ELF2 p.Ala444Gly Uncertain significance ★ ⚠ same type
ELF2 p.Ala517Ser Uncertain significance ★ ⚠ same type
ELF2 p.Ala541Thr 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/elf2-p-arg178cys (accessed [today's date]).

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