Is CSMD1 p.Phe2027= (c.6081C>T) pathogenic?

CSMD1 p.Phe2027= (c.6081C>T) is classified Benign in CSMD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Low-frequency (popmax 1.59%, afr).

How common is CSMD1 p.Phe2027= (c.6081C>T) in the general population?

CSMD1 p.Phe2027= (c.6081C>T) is low-frequency (popmax 1.59%, afr) (gnomAD).

CSMD1 p.Phe2027=

c.6081C>T · rs112571277 · VCV727306

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.59%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.04	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.1, phastCons 1
Overall
CADD	5.774	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.59% African / African-American · 1,193/75,026 alleles

Filtering AF 1.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.48%

Overall 0.0791% 1,276/1,613,984 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.59%	63
Remaining individualsnot grpmax-eligible	0.0768%	1,302
Admixed American	0.045%	2,223
European (non-Finnish)	0.000678%	147,486

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: CSMD1
Protein: p.Phe2027=
Coding: c.6081C>T
MANE Select: NM_033225
dbSNP: rs112571277
Type: single nucleotide variant
Location: chr8:3142625 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Residue 2027: the cub 12 domain

Full CSMD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSMD1 p.Ala1296Val Uncertain significance ★★ ⚠ same type
CSMD1 p.Asp908Ala Uncertain significance ★★ ⚠ same type
CSMD1 p.Asp927Asn Uncertain significance ★★ ⚠ same type
CSMD1 p.Gln308Leu Uncertain significance ★★ ⚠ same type
CSMD1 p.Glu1276Asp Uncertain significance ★★ ⚠ same type
CSMD1 p.Gly3156Arg Uncertain significance ★★ ⚠ same type
CSMD1 p.Ile1833Thr Uncertain significance ★★ ⚠ same type
CSMD1 p.Lys1718Asn 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/csmd1-p-phe2027 (accessed [today's date]).

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