Is ENAM p.Phe78= (c.234T>C) pathogenic?

ENAM p.Phe78= (c.234T>C) is classified Likely benign in ENAM (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-29). Rare (popmax 0.558%, afr); Associated with ENAM-related disorder.

What condition is associated with ENAM p.Phe78= (c.234T>C)?

ENAM p.Phe78= (c.234T>C) is associated with ENAM-related disorder (ClinVar).

How common is ENAM p.Phe78= (c.234T>C) in the general population?

ENAM p.Phe78= (c.234T>C) is rare (popmax 0.558%, afr) (gnomAD).

ENAM p.Phe78=

c.234T>C · rs34251790 · VCV3058802

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.558%, afr)

Conditions

ENAM-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.62	GERP 0.37, phastCons 0.057
Overall
CADD	1.568	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.558% African / African-American · 419/75,040 alleles

Filtering AF 0.514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.497%

Overall 0.0266% 430/1,614,150 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.558%	179
Remaining individualsnot grpmax-eligible	0.0112%	8,929
Admixed American	0.00333%	30,010
European (non-Finnish)	0.000169%	589,995

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: ENAM
Protein: p.Phe78=
Coding: c.234T>C
MANE Select: NM_031889
dbSNP: rs34251790
Type: single nucleotide variant
Location: chr4:70634331 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 36.63

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

Disease context

ENAM-related disorder

Similar variants

ENAM p.Phe78Ser Uncertain significance ★ ⚠ same residue
ENAM p.Glu218Ter Likely pathogenic ★ same condition
ENAM p.Ser723Arg Uncertain significance ★ ⚠ same condition
ENAM p.Gly342Glu Uncertain significance ⚠ same condition
ENAM p.Thr1070= Likely benign same condition
ENAM c.588+1del Pathogenic ★★ same condition
ENAM p.Pro422fs Pathogenic/Likely pathogenic ★★ same condition
ENAM p.Asn36fs Likely pathogenic ★ same condition

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/enam-p-phe78 (accessed [today's date]).

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