Is DHH p.Ser71= (c.213C>T) pathogenic?

DHH p.Ser71= (c.213C>T) is classified Likely benign in DHH (ClinVar, Single submitter, 2 submitters; last evaluated 2024-07-10). Very rare (popmax 0.00666%, afr).

How common is DHH p.Ser71= (c.213C>T) in the general population?

DHH p.Ser71= (c.213C>T) is very rare (popmax 0.00666%, afr) (gnomAD).

DHH p.Ser71=

c.213C>T · rs570786183 · VCV3049941

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00666%, afr)

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 -5	GERP -4.7
Overall
CADD	0.959	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00666% African / African-American · 5/75,044 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000434% 7/1,613,368 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00666%	15,009
Remaining individualsnot grpmax-eligible	0.0016%	62,504
South Asian	0.0011%	91,076

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: DHH
Protein: p.Ser71=
Coding: c.213C>T
MANE Select: NM_021044
dbSNP: rs570786183
Type: single nucleotide variant
Location: chr12:49094300 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB

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

Similar variants

DHH c.*401G>T Uncertain significance ★★ same type
DHH p.Ala287Glu Uncertain significance ★★ ⚠ same type
DHH p.Arg102His Uncertain significance ★★ ⚠ same type
DHH p.Arg309Leu Uncertain significance ★★ ⚠ same type
DHH p.Arg318Pro Uncertain significance ★★ ⚠ same type
DHH p.Ser210Arg Uncertain significance ★★ ⚠ same type
DHH c.303+66C>T Benign ★★ same type
DHH c.304-15T>C Likely benign ★★ 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/dhh-p-ser71 (accessed [today's date]).

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