Is INHA p.Ser148Ala (c.442T>G) pathogenic?

INHA p.Ser148Ala (c.442T>G) is classified Uncertain significance in INHA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.1402); Ultra-rare (popmax 0.0483%, amr).

How common is INHA p.Ser148Ala (c.442T>G) in the general population?

INHA p.Ser148Ala (c.442T>G) is ultra-rare (popmax 0.0483%, amr) (gnomAD).

What do computational predictors say about INHA p.Ser148Ala (c.442T>G)?

AlphaMissense predicts likely benign (score 0.1402) — an in-silico prediction, not a clinical call.

INHA p.Ser148Ala

c.442T>G · rs374088703 · VCV3109669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1402 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1402	likely benign
REVEL	0.412	indeterminate
SaProt	LLR -8.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,148 bp · p 0.17 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0483% Admixed American · 29/60,000 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0299%

Overall 0.00434% 70/1,613,942 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0483%	2,069
European (non-Finnish)	0.00331%	30,257
Remaining individualsnot grpmax-eligible	0.0032%	31,239

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.Ser148Ala
Coding: c.442T>G
MANE Select: NM_002191
dbSNP: rs374088703
Type: single nucleotide variant
Location: chr2:219574867 (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.Pro166= 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

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-ser148ala (accessed [today's date]).

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