Is HES7 p.Pro197= (c.591C>T) pathogenic?

HES7 p.Pro197= (c.591C>T) is classified Conflicting classifications of pathogenicity in HES7 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-17). Low-frequency (popmax 1.09%, mid).

How common is HES7 p.Pro197= (c.591C>T) in the general population?

HES7 p.Pro197= (c.591C>T) is low-frequency (popmax 1.09%, mid) (gnomAD).

HES7 p.Pro197=

c.591C>T · rs558811781 · VCV288808

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.09%, mid)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.2	phastCons 1
Overall
CADD	11.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.09% Middle Eastern · 39/3,564 alleles

Filtering AF 0.823% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.728%

Overall 0.121% 1,605/1,327,368 alleles · low-frequency exomes 1,104/1,175,178 · genomes 501/152,190 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.09%	91
African / African-American	0.79%	127
Admixed American	0.597%	167
Ashkenazi Jewishnot grpmax-eligible	0.291%	344
Remaining individualsnot grpmax-eligible	0.289%	346
European (non-Finnish)	0.0667%	1,500
South Asian	0.0145%	6,875
Finnishnot grpmax-eligible	0.00264%	37,884

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: HES7
Protein: p.Pro197=
Coding: c.591C>T
MANE Select: NM_001165967
dbSNP: rs558811781
Type: single nucleotide variant
Location: chr17:8121673 (GRCh38)

Full HES7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/hes7-p-pro197 (accessed [today's date]).

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