Is CHMP1A p.Phe115= (c.345C>T) pathogenic?

CHMP1A p.Phe115= (c.345C>T) is classified Likely benign in CHMP1A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). Very rare (popmax 0.00169%, amr).

How common is CHMP1A p.Phe115= (c.345C>T) in the general population?

CHMP1A p.Phe115= (c.345C>T) is very rare (popmax 0.00169%, amr) (gnomAD).

CHMP1A p.Phe115=

c.345C>T · rs747260304 · VCV2963914

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00169%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.7	GERP -3.4
Overall
CADD	6.334	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% Admixed American · 1/59,308 alleles

Filtering AF 0.000616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00124% 20/1,609,370 alleles · very rare exomes 16/1,457,194 · genomes 4/152,176 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00473%	21,132
Remaining individualsnot grpmax-eligible	0.00321%	31,144
Admixed Americangrpmax	0.00169%	59,308
South Asian	0.00111%	90,036
European (non-Finnish)	0.0011%	90,640

Finnish 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: CHMP1A
Protein: p.Phe115=
Coding: c.345C>T
MANE Select: NM_002768
dbSNP: rs747260304
Type: single nucleotide variant
Location: chr16:89647239 (GRCh38)
Gene constraint: LOEUF 1.045 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.44 · 4 PDB

Full CHMP1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHMP1A c.28-13G>A Pathogenic/Likely pathogenic ★★ same type
CHMP1A p.Ala172Thr Uncertain significance ★★ ⚠ same type
CHMP1A p.Arg46Cys Uncertain significance ★★ ⚠ same type
CHMP1A p.Arg54Cys Uncertain significance ★★ ⚠ same type
CHMP1A p.Arg64Trp Uncertain significance ★★ ⚠ same type
CHMP1A p.Cys44Ser Uncertain significance ★★ ⚠ same type
CHMP1A p.Gln186His Uncertain significance ★★ ⚠ same type
CHMP1A p.Gly59Ser 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/chmp1a-p-phe115 (accessed [today's date]).

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