Is EXPH5 p.Phe242= (c.726C>T) pathogenic?

EXPH5 p.Phe242= (c.726C>T) is classified Likely benign in EXPH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-29). Very rare (popmax 0.00223%, sas).

How common is EXPH5 p.Phe242= (c.726C>T) in the general population?

EXPH5 p.Phe242= (c.726C>T) is very rare (popmax 0.00223%, sas) (gnomAD).

EXPH5 p.Phe242=

c.726C>T · VCV4914019

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, sas)

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 3	GERP -1.1, phastCons 0.86
Overall
CADD	7.393	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% South Asian · 2/89,688 alleles

Filtering AF 0.00037% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000139%

Overall 0.000373% 6/1,608,670 alleles · very rare exomes 4/1,456,522 · genomes 2/152,148 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00223%	44,844
Admixed American	0.0017%	58,758
European (non-Finnish)	0.000255%	392,782

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: EXPH5
Protein: p.Phe242=
Coding: c.726C>T
MANE Select: NM_015065
Type: single nucleotide variant
Location: chr11:108514781 (GRCh38)
Gene constraint: LOEUF 1.142 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 36.39

Full EXPH5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EXPH5 p.Phe242Leu Benign ★ ⚠ same residue
EXPH5 p.Ala1429Ser Uncertain significance ★★ ⚠ same type
EXPH5 p.Arg1727Lys Uncertain significance ★★ ⚠ same type
EXPH5 p.Asn1548Asp Uncertain significance ★★ ⚠ same type
EXPH5 p.Asp741His Uncertain significance ★★ ⚠ same type
EXPH5 p.Gln1464Arg Uncertain significance ★★ ⚠ same type
EXPH5 p.Gly54Arg Uncertain significance ★★ ⚠ same type
EXPH5 p.Leu1519Arg 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/exph5-p-phe242 (accessed [today's date]).

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