Is EXPH5 p.Pro112= (c.336G>A) pathogenic?

EXPH5 p.Pro112= (c.336G>A) is classified Likely benign in EXPH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). Very rare (popmax 0.00798%, nfe).

How common is EXPH5 p.Pro112= (c.336G>A) in the general population?

EXPH5 p.Pro112= (c.336G>A) is very rare (popmax 0.00798%, nfe) (gnomAD).

EXPH5 p.Pro112=

c.336G>A · rs146999560 · VCV2642362

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00798%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.92	GERP -2.2
Overall
CADD	6.382	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00798% European (non-Finnish) · 94/1,177,776 alleles

Filtering AF 0.00665% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00617%

Overall 0.00627% 101/1,609,984 alleles · very rare exomes 92/1,458,004 · genomes 9/151,980 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00802%	12,465
European (non-Finnish)grpmax	0.00798%	12,530
East Asian	0.00223%	44,866
African / African-American	0.00134%	74,710

Remaining individuals 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: EXPH5
Protein: p.Pro112=
Coding: c.336G>A
MANE Select: NM_015065
dbSNP: rs146999560
Type: single nucleotide variant
Location: chr11:108539131 (GRCh38)
Gene constraint: LOEUF 1.142 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 36.39
Residue 112: the 'disordered' region

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

Similar variants

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
EXPH5 p.Leu234Phe 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-pro112 (accessed [today's date]).

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