Is INHA p.Pro166= (c.498C>T) pathogenic?

INHA p.Pro166= (c.498C>T) is classified Likely benign in INHA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-23). Ultra-rare (popmax 0.0825%, mid).

How common is INHA p.Pro166= (c.498C>T) in the general population?

INHA p.Pro166= (c.498C>T) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

INHA p.Pro166=

c.498C>T · rs145398632 · VCV754643

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, 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 -1.3	GERP -2.5
Overall
CADD	1.816	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% Middle Eastern · 5/6,062 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.011% 178/1,614,206 alleles · ultra-rare exomes 166/1,461,828 · genomes 12/152,378 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
Finnishnot grpmax-eligible	0.0344%	2,909
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Admixed American	0.015%	6,671
European (non-Finnish)	0.0108%	9,219

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: INHA
Protein: p.Pro166=
Coding: c.498C>T
MANE Select: NM_002191
dbSNP: rs145398632
Type: single nucleotide variant
Location: chr2:219574923 (GRCh38)
Gene constraint: LOEUF 0.686 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 70.80

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

Similar variants

INHA p.Ala257Thr Benign/Likely benign ★★ same type
INHA p.Gly109= Benign ★★ same type
INHA p.Gly65= Benign/Likely benign ★★ same type
INHA p.Ala144Val Uncertain significance ★ ⚠ same type
INHA p.Ala207Thr Uncertain significance ★ ⚠ same type
INHA p.Ala45Thr Uncertain significance ★ ⚠ same type
INHA p.Ala63Val Uncertain significance ★ ⚠ same type
INHA p.Arg116Trp 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/inha-p-pro166 (accessed [today's date]).

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