Is DHRS7B p.Phe35= (c.105C>T) pathogenic?

DHRS7B p.Phe35= (c.105C>T) is classified Likely benign in DHRS7B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Ultra-rare (popmax 0.0165%, mid).

How common is DHRS7B p.Phe35= (c.105C>T) in the general population?

DHRS7B p.Phe35= (c.105C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

DHRS7B p.Phe35=

c.105C>T · rs181347227 · VCV2647573

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -1.5	GERP -8.4
Overall
CADD	7.385	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00622% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.0018% 29/1,614,152 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
East Asian	0.0134%	7,481
African / African-American	0.012%	8,340
Remaining individualsnot grpmax-eligible	0.0016%	62,510
South Asian	0.0011%	91,072
European (non-Finnish)	0.000932%	107,273

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: DHRS7B
Protein: p.Phe35=
Coding: c.105C>T
MANE Select: NM_015510
dbSNP: rs181347227
Type: single nucleotide variant
Location: chr17:21172102 (GRCh38)
Gene constraint: LOEUF 1.179 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.82

Full DHRS7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DHRS7B p.Ala208Gly Uncertain significance ★ ⚠ same type
DHRS7B p.Ala213Ser Uncertain significance ★ ⚠ same type
DHRS7B p.Ala213Thr Uncertain significance ★ ⚠ same type
DHRS7B p.Ala251Thr Uncertain significance ★ ⚠ same type
DHRS7B p.Ala251Val Uncertain significance ★ ⚠ same type
DHRS7B p.Ala273Gly Uncertain significance ★ ⚠ same type
DHRS7B p.Ala75Val Uncertain significance ★ ⚠ same type
DHRS7B p.Arg148Cys 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/dhrs7b-p-phe35 (accessed [today's date]).

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